Ebook: Exercise Physiology: from a Cellular to an Integrative Approach

The first textbook in exercise physiology has been published by Ferdinand Lagrange, Physiology of Bodily Exercise in 1889. Since that time, many unresolved issues have been challenged and the body of knowledge continues growing every day. The recent emergence of exercise biochemistry makes the field of exercise physiology even more complex and exciting and open new ways in the understanding of exercise, performance and health.

This handbook does not cover the entire field of exercise physiology and we try to make originality in mixing continuously both the integrative approach of physiology and the biocellular approach all along the book. Nine topics are described and discussed in the present handbook.

The book starts with three classical sections: muscle activity, respiration and cardiac physiology; with chapters dealing with general structure and functions, and chapters incorporating very updated information.

The fourth section is devoted to blood flow dynamics, blood circulation and vascular function and include some chapters that are rarely addressed in exercise physiology books, such as the influences of exercise on endothelium, vasomotor control mechanisms, coagulation, immune function and rheological properties of blood, and their influences on hemodynamics.

The sections five and six focused on the different methodological and technical ways to evaluate the aerobic and anaerobic fitness, and discussed the underlying concepts and utilities (for performance and health) of the different existing exercise tests.

The seventh and eighth sections deal with examples of environmental physiology and some causes of exercise sudden death in apparently healthy subjects.

In 1855, a physician named William H. Byford who was very interested in the healthfulness effects of exercise wondered why, for the most part, both the medical and physical education professions were largely unconcerned with exercise physiology. In an article entitled On the Physiology of Exercise in the American Journal of Medical Sciences, he noted that “Although the Importance of voluntary exercise has been recognized for centuries and prescribed to its most useful extent by many of the profession, its great practical advantages in a large number of diseases have not been appreciated to their full extent of all […] It is with a view to draw the attention of the profession to the importance of more research in this direction, that I wish to record my views upon the subject”. Fortunately, progress have been made in this area and although exercise rehabilitation programs are not easily available in every country of the world, more and more data comforts the fact that regular physical activity is a good way to improve health in disease or to prevent the appearance of diseases. The section nine is therefore logically devoted to the beneficial effects of exercise rehabilitation on ageing and different kind of diseases such as metabolic, respiratory, cardiovascular, hematological or viral diseases, and cancer. In addition, this section also discusses the usefulness of exercise testing to diagnose a disease or follow the effects of therapeutic interventions for a given disease.

This book is intended for advanced undergraduates with strong science backgrounds, researchers, physiologist and physician involved in the area of exercise physiology.

Philippe Connes, Olivier Hue, Stéphane Perrey

Skeletal muscle consists of muscle fibers, each of which is a multi-nucleated cylindrical cell. There are two kinds of skeletal muscle fibers: fast-twitch fibers (type II) and slow-twitch fibers (type I). Type II fibers are further classified into 3 categories: IIA, IID and IIB. Their speed of contraction is IIB>IID>IIA>I. Their common energy source is ATP. In fast-twitch fibers, ATP is generated by glycolysis, hence rich in glycogen granules. In slow twitch fibers, ATP is generated from oxidative phosphorylation, hence rich in mitochondria. Type IIA fibers depend on both. The fast-twitch fibers are used for quick movement, and slow-twitch fibers are used for sustained contraction. The number of fibers activated increases with exercise intensity. Type I fibers are the first to be recruited followed by type II fibers.

Sarcomere is a subcellular organelle, and defines the unit of contraction. It is composed of interdigitating thick and thin filaments. The major component of the thick filament is myosin with mw of ~500 kD. Additional components are C-protein and titin (also called connectin), which wrap around the thick filament. The major component of the thin filament is actin. The interaction between actin and myosin generates force, which is transmitted to the next sarcomere and eventually to a skeleton. The interaction is regulated by Ca²⁺ via tropomyosin (Tm) and troponin (Tn). There is a positive feedback mechanism called “cooperativity” between myosin, actin, Tm and Tn: Tm allosterically affects actin to improve actin-myosin interaction; the interaction of actin and myosin enhances Tm binding to actin, etc. Such a system turns on quickly, whereas it turns off in a caotic manner.

The molecular domain which projects from myosin to actin is called cross-bridges. With a repetitive attachment and detachment of cross-bridges, filament sliding occurs to generate force and perform work. This is called the cross-bridge cycle, and it goes through several intermediate steps. Each step is called an elementary step, which includes ATP-binding step, ATP-cleavage step, phosphate(Pi)-release step, and ADP-release step. The binding/release steps are preceded (or post-ceded) by a conformational change in the actomyosin complex. We now know that the conformational change which precedes Pi-release is the step that generates force.

A single bout of contractile activity produces a multitude of time- and intensity-dependent hormonal and cellular perturbations within skeletal muscle. With the onset of contractile activity, cytosolic and mitochondrial [Ca²⁺] levels are rapidly increased and, depending on the relative intensity of the exercise, metabolite concentrations change. These contraction-induced metabolic disturbances activate several key kinases and phosphatases involved in signal transduction. Chief among these are the calcium-dependent signalling pathways that respond to elevated Ca²⁺ concentrations (including Ca²⁺/calmodulin-dependent kinase [CaMK], Ca²⁺-dependent protein kinase C [PKC] and the Ca²⁺/calmodulin-dependent phosphatase calcineurin); the 5'-adenosine monophosphate-activated protein kinase (AMPK), several of the mitogen-activated protein kinases (MAPK), and protein kinase B/Akt. In addition, there are exercise-induced central nervous system (CNS) stimulatory effects on various hormones and endocrine organs that promote the oxidation of carbohydrate-based fuels. With repeated bouts of contractile activity (i.e. exercise training) there are numerous and coordinated biochemical adaptations in skeletal muscle that decrease the reliance on carbohydrate-based fuels and enhance the oxidation of lipid-based fuels via reduced sympathetic nervous system responses to any given submaximal exercise intensity. These adaptations serve to minimize cellular disturbances during subsequent exercise bouts. Accordingly, chronic adaptations in skeletal muscle are likely to be the result of the cumulative effects of repeated bouts of exercise, with the initial signaling responses leading to such adaptations occurring after each (acute) training session. This chapter will summarize our current understanding of the hormonal and cellular control of bioenergetics in human skeletal muscle.

The force producing capability of skeletal muscle is regulated by a number of simultaneously occurring processes that provide real-time fine tuning of contractility. This allows for the locomotory demands of the individual to attempt to be met within functional confines of contracting muscle that change as exercise progresses. Fatigue occurs in response to high-intensity exercise, as well as during prolonged low-intensity exercise, although the ionic and metabolic factors contributing to these two types of fatigue may differ. Fatigue of high-intensity exercise is recognized to occur primarily by depression and failure of excitability, either at the sarcolemmal or perhaps within the t-tubule system, due to altered electrico-chemical gradients for K⁺, Cl^- and Na⁺. There is increasing evidence that increased intra- and extracellular [H⁺] and [lactate^-] help to stabilize the sarcolemma and help to maintain excitability. The fatigue of prolonged, low-intensity exercise may be characterized by depletion of energy substrate, primarily glycogen, and a decreased intracellular [K⁺] with ensuing depressed membrane excitability may also contribute. Both types of fatigue are also associated with increased concentrations of reactive oxygen species (ROS), and increased [ROS] appears to downregulate the activities of key ion transporting and metabolic enzymes, as well as contributing to muscle damage in the long term. The purpose of this chapter is to provide an overview of our current knowledge and speculations regarding these main contributors to skeletal muscle fatigue.

Since the first experiment on isolated muscle in 1974, phosphorus-31 nuclear magnetic resonance spectroscopy (³¹P-MRS) has become widely accepted as the “gold standard” method for non-invasive measurements of energy metabolism in exercising muscle. The scope of the present review is related to the metabolic changes occurring in human exercising muscle and to the metabolic effects of training as recorded using ³¹P MRS. ³¹P-MRS investigation of exercising muscle requires by definition the utilisation of dedicated ergometers allowing on the one hand to perform an exercise inside a superconducting magnet and on the other hand accurate measurement of power output.

The specificity of the training stimulus is related to its type which can be classified as resistance or endurance training. MR studies have initially been devoted to the comparative analysis of high-energy phosphate metabolites at rest in order to provide information about changes in fiber type composition after endurance or resistance training while ¹H MR imaging (MRI) gave additional information regarding alteration in muscle volume. Increased in proportion of type II fibers induced by resistance training was associated with an elevated PCr/Pi and PCr/ATP_β ratios whereas opposite effects were reported after endurance training.

Another fruitful approach has been related to changes in ATP producing mechanisms (oxidative vs anaerobic) and muscle energy cost as a result of training. Energy cost was significantly higher in resistance-trained as compared to sedentary and endurance trained subjects. Resistance-trained subjects also exhibited an increased contribution from PCr and glycolysis to ATP production whereas this contribution was significantly decreased in endurance-trained subjects. Rather than an improvement in energy cost, endurance training seems to be favour exercise performance through changes in ATP-producing mechanisms. On the contrary, resistance training effects are clearly related to alteration in fiber type composition.

In this review, we will also consider improvement in mitochondrial function after endurance training and the role of O₂ supply as a limiting factor in endurance-trained and sedentary subjects.

To adequately respond to the metabolic demand during exercise, the respiratory system has to closely regulate the ventilatory and the cardiovascular systems.

After a brief description of the anatomy of lungs, pleura, thoracic cage, and respiratory muscles, the attention is focused on the mechanics of breathing.

The second part of the chapter is devoted to the mechanics of breathing. In other words, the questions are: what are the strengths able to deform the rib cage and how are they exerted on the lungs, generating flow and volume changes?

The first part of this section defines pressures (pleural, alveolar, intra-thoracic, and trans-thoracic pressures), flows, and volumes, and their respective ratios (i.e. volume/pressure and flow/pressure curves), to explain the effects of compliance (of lung, thorax, and respiratory system) and resistance (of airways, or respiratory tissues) on respiratory movements and ventilation. In a second part, classical representations of spirometry are introduced, as well as representations of the volume/pressure, flow/volume, during both tidal ventilation and ventilation during exercise.

In healthy humans at sea level, alveolar ventilation is precisely regulated to match metabolic rate and maintain pH and arterial partial pressure of dioxygen (O₂) and carbon dioxide (CO₂) at, or close to, resting levels over a wide range of workloads. However, the mechanism that links ventilation to O₂ demand and metabolic CO₂ production remains highly controversial.

The control system that allows regulation of ventilation during exercise with such precision and efficiency consists of three highly integrative levels of control: 1) the central respiratory rhythm and pattern generator (central respiratory controller), 2) distribution and synchronization of respiratory motor output to the appropriate respiratory muscles, and 3) sensory inputs of both peripheral and central origin.

Although controversy remains regarding the primary mechanism regulating exercise hyperpnea, feedback from the active muscles and central command (feedforward) are powerful stimuli capable of substantially modulating the activity of the central respiratory controller and likely contribute to a significant extent to hyperpnea. We propose that these mechanisms dynamically interact to produce adequate ventilation regarding metabolic and gas exchange rates during exercise, with the carotid chemoreceptor adapting the ventilatory response to small changes in arterial CO₂ and acidosis.

The lung derives from two distinct embryonic origins, has two separate circulations, undergoes extensive branching morphogenesis, experiences the highest blood flow and the largest continuous distortion among organs due to wide fluctuations in ventilation, perfusion and mechanical stresses. The inflated lung volume consists of about 85% air and 15% cells, fibers, matrix and blood. Both gravitation-dependent and -independent gradients contribute to spatial heterogeneity in structure and function. Dynamic factors such as surface folding, the surfactant layer, and capillary erythrocytes distribution greatly influence the physical properties of the organ. These unique features pose challenges for the optimization of lung function in health and disease. Oxygen uptake across the lung begins with O₂ flow into the lungs via negative pressure generated by diaphragm contraction, followed by convective distribution among airways, diffusive distribution within intra-acinar air spaces and across the blood-gas barrier, diffusion across plasma and capillary erythrocyte membrane and finally chemical reaction with hemoglobin. Efficiency of O₂ transfer depends on appropriate matching between diffusion interfaces, allosteric interaction with hemoglobin, and regulation of hematological volumes and flow. This chapter briefly reviews: 1. Structural determinants of gas exchange. 2. Physiological determinants of gas exchange, including distributive and diffusive factors, the methods of measurement and interpretation of results. 3. Arterial oxygen homeostasis, including optimization of alveolar-arterial O₂ tension gradient during exercise via regulation of hematological volumes and allosteric control of the oxyhemoglobin dissociation curve.

Performance of the cardiovascular system is one of the primary determinants of exercise potential. Coordinated biventricular function with the ability to augment of cardiac output underlies the ability to obtain normal and supra-normal levels of peak exercise capacity. This chapter will provide an overview of cardiac structure and function as it relates to exercise capacity. Specifically, characteristics of both the left and right ventricle will discussed with emphasis on their differential structure and function during physical activity. Mechanisms of contraction, relaxation, and chronotropic function during exercise and at rest in sedentary individuals and in trained athlete will be reviewed. Next, we will address the established findings and the areas of uncertainty regarding how the heart responds to exercise training and deconditioning. Focus topics will include structural change, functional adaptation, and underlying cellular modifications. Finally, a brief discussion about the impact and causality of intrinsic structural heart disease on exercise capacity limitations will be provided.

In this chapter I will present the ECG physiological basis (cellular action potential, ECG acquisition and representation). I will show the ECG adaptations during acute exercise and I think that it will be interesting to present the main ECG adaptations and their limits observed in the so called Athlete's heart.

Cardiac performance is a major determinant of aerobic fitness. It depends on cardiac output that can be varied by changes in stroke volume (SV) and heart rate (HR). SV is driven by numerous factors such as loading conditions (i.e. preload and afterload) and intrinsic myocardial properties (i.e. contractility, relaxation). During exercise, cardiac sympathetic activity increases HR and both ventricular contractility and relaxation. Venous return increases, due to both sympathetic vasomotor nerves that induces venoconstriction in the splanchnic circulation and skelatal muscle contractions that compress veins in the limbs. Moreover, afterload decreases consequently to the vasodilation in the exercise skeletal muscles that induces a fall in systemic vascular resistances. Human studies observed that, as a result of these adaptations within the heart and outside it, SV increases from rest to submaximal exercise (about 50 of maximal aerobic power), and then remains constant from submaximal to maximal exercise, that can be explained by a lower LV filling time compensated by a higher myocardial contractility. HR increases in proportion to oxygen consumption and reaches a maximum of about 180–200 beat per minute during maximal exercise in young adults. The changes in SV and HR result in a drop of cardiac output from 4–7 L. min⁻¹ at rest to 15–20 L. min⁻¹. Cardiac performance can be improved by aerobic training. At rest, trained subjects exhibited a cardiac enlagement named as “athlete's heart” and including increases in LV chamber size and wall thickness. LV systolic function appears to be normal in athletes, both when measured at rest and during exercise. LV diastolic function is on average normal at rest, but enhanced during exercise wich favours adequate filling of the LV at high heart rate. These adaptations result in a higher cardiac reserve during effort in athletes. On overall, cardiac performance during exercise has been evaluated mainly using hemodynamics parameters such as mitral filling patterns or ejection fraction. New non-invasive tools based on Doppler echocardiography (e.g. Tissue Doppler or speckle tracking imaging) and cardiac magnetic resonnance imaging have the potential to evaluate intrinsic myocardial performance in the future.

The exploration of heart rate variability (HRV) for clinical purposes in medical sciences as well as for follow-up and monitoring the effects of training in exercise sciences has gained increased popularity in the recent years.

The technique is simple, non invasive, and allows an exploration of Autonomic Nervous System (ANS) activity based on the recording of successive heart beats. Usually measured overnight, over 24h or 5 minutes, the HRV indices can be calculated using time-domain, frequency-domain (Fast Fourier Transform), time-frequency domain (Wavelets) or geometrical as well as Poincaré analysis. These obtained indices reflect global autonomic activity, sympathetic and parasympathetic activity.

HRV indices have proved to be valuable markers of the evolution of the disease or pathological states. Moreover, they have also been associated to good or bad fitness status or performance achievement, which led to the wide use of HRV indices to monitor the effects of training on fitness, fatigue and performance prediction. Indeed, both at a group and at an individual level, HRV indices evolved negatively with heavy cumulated training loads. Inversely, their positive evolution during tapering periods were associated with better performance achievement: the higher the ANS activity, the better the performance. ANS monitoring is thus useful on the short term, on a daily basis, as well as on the long term, on months and years.

Besides, the application of HRV indices in training monitoring opened the exploration of ANS activity in the context of overtraining evolution and thus, prevention. The constant decrease in sympathetic and/or parasympathetic as well as global ANS activity with important cumulated training loads, associated with a lack of reincrease during recovery periods, led to the hypothesis of a possible evolution of overreaching to overtraining through a successive step down of sympathetic and parasympathetic activity. This lower activity of the ANS seems coherent with the numerous clinical syndromes associated with overtraining and could thus be a determinant background of the overtraining state.

This introductory chapter for Section 4 will overview the anatomical, histological and functional characteristics of the vascular system and will briefly review the physical principles governing blood flow in various sections of the circulatory system.

The first part of this chapter will review the anatomical and histological characteristics of blood vessels, including arteries, arterioles, capillaries, postcapillary venules and veins. Particular emphasis will be on exploring the strikingly close correlation between their wall structure and physiological function of transporting and distributing oxygen and other essential substances to the tissues and also removing by-products of metabolism.

The second part of the chapter will review the progressive changes of luminal diameter and vascular cross-sectional area along the circulatory system. The consequent changes in intravascular pressure, vascular resistance, wall shear stress and blood flow dynamics will be discussed, also highlighting the critical importance of the macro- and microrheological properties of blood. In addition, the chapter will introduce some basic physical principles governing nutritional exchange between tissues and the vascular channels (i.e., Starling law).

The concluding part of the chapter, as a transition to chapter 4.2, will highlight the critical importance of vascular control mechanisms responsible for altering blood flow distribution necessary to meet the ever changing tissue requirements in response to physiologic and pathologic conditions.

The control of skeletal muscle resistance vessel tone is critical for 1) the regulation of muscle tissue oxygenation to support continued metabolic and contractile activity, and 2) regulation of arterial blood pressure. With regard to muscle oxygenation, vasodilatation is often capable of a remarkably tight matching of increases in muscle blood flow (oxygen delivery) with increases in metabolic demand. Rapid onset vasodilator mechanisms likely related to muscle activation and mechanical distortion can initiate increases in muscle blood flow with the first contraction of exercise. This initial response can be complete within 5-10 seconds and often, though not always, constitutes the majority of the blood flow increase with exercise. Slower onset “feedback” mechanisms related to muscle metabolism and oxygenation are thought to achieve final matching of muscle blood flow to metabolic demand. This matching can be uncoupled however, since exercising muscle blood flow does not recover to steady state levels when local perfusion pressure is altered. With regard to blood pressure regulation, the capacity of skeletal muscle to increase metabolic activity far surpasses that of any other tissue. The muscle blood flow required to match this demand can challenge and even surpass the pumping capacity of the heart. Given that the arterial baroreflex is reset to higher levels with increasing exercise intensity and relies primarily on vasoconstriction in regulating blood pressure, this necessitates that muscle resistance vessels become a critical target for sympathetic neural vasoconstriction as part of arterial blood pressure regulation. Therefore, control of skeletal muscle resistance vessels in exercise integrates the competing requirements for regulation of muscle oxygenation and regulation of arterial blood pressure. While arterial blood pressure ultimately takes precedence, local factors in exercising muscle can reduce responsiveness to sympathetic vasoconstriction in accordance with local metabolic demand. This is known as “functional” sympatholysis. Current concepts propose that this may optimize the balance between vasoconstrictor and vasodilator influences across exercising muscles. The result is that sympathetic neural restraint of exercising muscle blood flow is minimized while arterial blood pressure regulation is maintained.

Hemorheology is the science of the deformation and flow of blood and its formed elements (mainly red blood cells and to a lesser part white blood cells and platelets). This field includes investigating the bulk properties of blood, determined in viscometric experiments in macroscopic samples, and its microscopic properties. The present review will first consider the known and postulated effects of blood rheological properties on aerobic performance as related to its effects on oxygen delivery and second, the acute and long term effects of exercise on blood rheology. Blood and plasma viscosities are among main determinants of blood flow resistance both in macro- and microcirculation and of cardiac function. Red blood cell (RBC) deformability and local hematocrit have also been demonstrated to influence the oxygen diffusion capacity at the pulmonary and the muscular levels. At least, RBC aggregation properties may have either a negative or positive effect on blood flow, and thus on aerobic performance, depending on the orientation of the vessels, the shear rate in those vessels and the interaction of RBC aggregates with endothelium. During exercise, plasma viscosity and hematocrit usually increase leading to an increase of blood viscosity. Controversial results are frequently found about the influence of acute exercise on RBC deformability and aggregation, with some studies describing alterations, improvement or no changes, depending on the kind of exercise performed and on the population studied. The mechanisms underlying these changes might be attributed to white cell activation and/or lactic acid production. Also, we will discuss the effects of training, with aerobic training decreasing blood and plasma viscosities, lowering hematocrit and RBC aggregation, increasing RBC deformability.

Endothelium serves as the permeability barrier between the blood and interstitial space. Endothelial function includes the production, secretion and metabolisation of bio-active molecules. Endothelium also plays significant roles in cell migration, remodeling of the vasculature (including proliferation and apoptosis). Finally, endothelial function is an important effector in the regulatory processes of vascular tonus which in turn determines the flow resistance. The role of hemodynamic shear forces in modulating the endothelial function is now well established. Cardiac output and flow rate in the vasculature significantly increases during exercise, resulting in enhanced wall shear stress affecting on the endothelium. Alterations in endothelial function were demonstrated in response to various exercise protocols in human beings and also in various experimental animals. Blood rheology may also be affected by acute exercise episodes and training, with the potential of modulating endothelial function.

This chapter will focus on the description of endothelial functions, role of wall shear stress in modulating these functions, hemodynamic and hemorheological determinants of wall shear stress in relation of endothelial function and finally review the literature on the modifications of endothelial functions in relation to exercise.

Acute inflammation constitutes a very well-organized response to any type of tissue damage engaging multiple systems such as the blood clotting mechanism, complement activation and the immune system, aiming in tissue repair and ultimately it's healing. Strenuous exercise is accompanied by muscle cell damage which is associated with inflammation (increase of cytokines, adhesion molecules, microparticles and neutrophils) in order to repair damaged tissues. It has been documented that acute exercise causes a biphasic leukocytosis consisting of an immediate and a delayed activation of lymphocytes, neutrophils, and macrophages. Free radicals generated by neutrophils and macrophages are vital in clearing away muscle tissue that has been damaged by exercise but they may also cause propagation of tissue damage. Neutrophils form the superoxide radical through the reaction of an enzyme called NADPH oxidase which is located in their plasma membrane. Although previous research has focused on the detrimental effects of free radicals (i.e. oxidative stress, aging, disease pathogenesis), there is mounting evidence now that free radicals may serve as useful signalling molecules to regulate cell growth, differentiation, proliferation, and death. Inflammation significantly changes cellular redox status by promoting a prooxidative response through immune cell infiltration to the damaged muscle cells while at the same time antioxidant adaptations permit the selective expression of antioxidant to keep the inflammatory response under control. Increasing evidence suggest that redox-sensitive signalling pathways, mainly NFkB, MAPK, and AP-1, have a prominent role in the regulation of muscle damage-induced inflammation through upregulation of both oxidative stress and antioxidants. In addition, homeostasis of reduced and oxidized glutathione (GSH:GSSG) appears to be crucial in redox signalling and overall control of the inflammation process. The present chapter examines the role of free radicals in redox signalling during exercise-induced inflammation and presents data regarding the potential role of long-term exercise training and antioxidant supplementation towards the protection against exercise-induced inflammation.

Activation of coagulation and fibrinolysis occur in exercise. Available evidence suggests that strenuous exercise induce activation of blood coagulation with concomitant enhancement of blood fibrinolysis men, women and adolescents. Although the responses of blood coagulation and fibrinolysis appear to be related to the exercise intensity and duration, recent reports suggests that moderate exercise intensity is followed by activation of blood fibrinolysis without simultaneous hyper-coagulability, while very intense exercise is associated with concurrent activation of blood coagulation and fibrinolysis. Exercise effects on platelet aggregation and function in healthy individuals have produced conflicting results. However for patients with history of coronary heart disease, the preponderance of available evidence would suggest that platelet aggregation and functions are increased with exercise. Meagre information exists on the effect of exercise training on blood coagulation and fibrinolysis and the exact effects are not as yet known. Recent reports suggest that training-associated improvement in markers of endogenous fibrinolysis appear to be related to the intensity and duration of the training programme. Although the effects of physical training on platelets have been briefly investigated, the evidence reported recently suggests that exercise training is linked with favourable effects on platelet aggregation and activation in both men and women.

Several concepts have emerged related to endurance exercise performance and the first component issue is the level of aerobic metabolism that can be maintained during a race. The upper limit for this is maximal oxygen uptake (VO2max). This is usually achieved during relatively large muscle mass exercise and represents the integrative ability of the heart to generate a high cardiac output, total body haemoglobin, high muscle blood flow and muscle oxygen extraction. VO2 max is an important determinant of endurance performance which represents a true parametric measure of cardiorespiratory capacity for an individual at a given degree of fitness and oxygen availability. VO2 max values 50–100% greater than those seen in normally active healthy young subjects are seen in champion endurance athletes and the most adaptations to training that contribute to these high VO2 max values include increased cardiac stroke volume, increased blood volume, increased capillary density and mitochondrial density in the trained muscles. The primary distinguishing characteristic of elite endurance athletes that allows them to exercise fast over prolonged periods of time is a large, compliant heart with a compliant pericardium that can accommodate a lot of blood, very fast, to take maximal advantage of the Starling mechanism to generate a large stroke volume.

Why athletes stop exercising at VO2 max? Among some mechanisms presented in the literature, actual evidence show that severe functional alterations appear at the local muscle level due to what is ultimately a limitation in convective oxygen transport, which activates muscle afferents leading to cessation of central motor drive and voluntary effort.

Pulmonary oxygen uptake (VO2) measurements, though not without problems of data collection, analysis and interpretation, can provide valuable insights into metabolic control processes within exercising muscle. The primary component of VO2 kinetics gives a faithful representation of muscle VO2. One of the long-lasting debates in the field concerns whether or not the time constant of the primary component is slower for work rates above the lactate threshold (LT) compared to those below the LT. At these high work rates, a VO2 slow component manifests and is responsible for increasing the total metabolic O2 gain. The slow component phenomenon challenges some of the fundamental concepts in exercise physiology including the notion of steady-state VO2, O2 deficit, work efficiency and the control of muscle energetics. Mechanistic bases of this phenomenon are crucial to our understanding of muscle function and dysfunction. The VO2 slow component represents an excess VO2 that mandate an accelerated glycogenolysis which accelerate the fatigue processes. Slower VO2 kinetics obligate an increased O2 deficit and greater perturbation of the intracellular milieu that is accompanied by reduced exercise tolerance. Interventions that facilitate either a speeding of the VO2 response towards the expected steady state or a reduction in the magnitude of the VO2 slow component should therefore result in improved exercise tolerance. Augmented O2 delivery can speed the overall VO2 kinetics, increase the gain of the VO2 primary component and reduce the VO2 slow component. The most potent intervention is endurance exercise training. On a practical note, although a large number of studies have demonstrated that endurance training results in improved VO2 kinetics, the actual type (volume, intensity, frequency and duration) that optimise these effects remains to be elucidated.

It appears that the rate and magnitude of improvement in VO2 max and VO2 kinetics with training may be dissociated, suggesting different mechanisms.

More than 200 years ago lactate and oxygen had been identified as important chemical components and shortly later they were linked with metabolism and physical activity. Compared to these roots, threshold concepts as measures of aerobic fitness are relative recent developments invented during the second half of the last century. All thresholds are based on specific patterns of individual or combined increases in measures such as lactate, oxygen uptake, carbon dioxide production and ventilation during exercise tests with an increasing workload. Thresholds are supposed to identify objectively the transition from one to another metabolic state related to aerobic and anaerobic components of energy metabolism. They are useful measures of aerobic fitness and may monitor selected adaptations to training more sensitively than the maximum oxygen uptake. However, different threshold concepts and testing procedures provide different estimates of aerobic fitness, which are not directly comparable. The maximal lactate steady state is no unique threshold concept. It shall indicate the highest prolonged constant workload that can be sustained without anaerobic energy. At higher exercise intensity some anaerobic energy is required as indicated by a continuous increase in lactate over time whilst the workload is kept constant. The maximal lactate steady state has been used to validate selected threshold concepts. Workloads detected by most threshold concepts and the maximal lactate steady state are equally well correlated with best performances in testing and competition, and with multiple exercise intensities predicted or observed in prospective or observatory training studies. However, there is no evidence that any specific threshold or the maximal lactate steady state directly predicts an optimal training load. There is a vital need for multi-disciplinary integrative and applied research to close the increasing gap between the rapid growth in the understanding of factors and mechanisms regulating and limiting metabolism on cellular and molecular level and the corresponding complex interplay of effects on whole body performance and non- and minimal invasive measures of physiological acute responses.