Exercise physiology and training principles

Respiratory

Cardiovascular

A detailed description of the cardiovascular system is beyond the scope of this book, and readers are referred to the numerous excellent textbooks on cardiovascular physiology for a comprehensive description of cardiovascular structure and function (e.g., Levick, 2009). The following section provides an overview of the integrated response of the cardiovascular system to exercise.

Definition of fatigue

Even agreeing upon a definition of fatigue has proved elusive – not least because its presence, or otherwise, can be specific to the test, timing and conditions used to detect it. For example, changes in muscle responses to electrical stimulation can differ at different stimulation frequencies such that ‘fatigue’ is revealed only at the ‘right’ frequency. Similarly, any definition of fatigue must recognize that force-generating capacity is not the only muscle property that is affected by the process of fatigue; reductions in muscle power and speed are also indicators of fatigue (see below). Early definitions were oversimplistic, relying upon measurement of isometric force, e.g., ‘the inability to maintain the required or expected force’ (Bigland-Ritchie, 1981). This is not to imply that such definitions are invalid; indeed, this definition is used extensively in the literature as a method to identify respiratory muscle fatigue and to test its relationship to exercise tolerance (Romer & Polkey, 2008). However, this definition is limited and, in 1992, Enoka & Stuart proposed the following definition of fatigue, which encapsulates a number of important characteristics of fatigue that previous definitions had neglected: ‘an acute impairment of performance that includes both an increase in the perceived effort necessary to exert a desired force and an eventual inability to produce this force’ (Enoka & Stuart, 1992). Although Enoka & Stuart's 1992 definition still focuses upon force as the outcome measure of function, it acknowledges a number of important features of fatigue: (1) the transiency of fatigue, (2) that fatigue can be manifested during movements (not just isometric contractions), (3) that fatigue is associated with sensations, and (4) that fatigue is a process (not an end point). However, although this definition hints at the fact that fatigue can be present before performance declines, and / or task failure occurs, it is not explicit. This important concept is explored in the section ‘Task failure and task dependency’

Indicators of fatigue

For reasons of technical expediency, laboratory studies of fatigue have tended to focus upon measurement of isometric force in the identification of fatigue. These contractions are used to both induce and to measure a decline in function. When asked to maintain a maximal isometric contraction of a limb muscle, with biofeedback of force and encouragement, people can typically sustain the contraction for around a minute. Over the course of the minute, force declines progressively and muscle discomfort rises. Eventually there is an almost complete loss of force, which is followed swiftly by intolerance and cessation of contraction. The difficulty with tests such as this is two-fold: (1) they are not physiological, and (2) it is impossible to distinguish loss of force due to declining effort from loss due to declining function. One way to overcome the second issue is to stimulate the muscle briefly with an electrical stimulus to assess the contractile state of the muscle per se. However, this process is not without its own limitations (see above), and also does not distinguish between decline in effort and decline in the motor drive to the muscle from the spinal cord and brain. Notwithstanding this, electrical stimulation experiments have revealed that fatigue at the level of the contractile machinery is not only associated with a decline in maximal force, it is also associated with slowing of the rate of force development and the rate of relaxation (Cady et al, 1989). Since muscle power is the product of force and speed of contraction, it is obvious that fatigue is associated with a loss of muscle power output.

As should be apparent from the preceding paragraph, exercise-induced decline in muscle functional properties (fatigue) can be due to failure at the level of the contractile machinery, or to failure of nervous system activation of muscle contraction. Inevitably, this influences the techniques used to identify the presence of fatigue and their limitations. The following section considers the potential sites of fatigue, before moving on to consider some of the underlying mechanisms.

Potential sites and causes of fatigue

In 1981, Brenda Bigland-Ritchie published a model that identified a number of potential sites / factors influencing fatigue, extending from the motor cortex to the muscle contractile machinery; it also included the influence of the supply the energy for interaction between the contractile proteins (Bigland-Ritchie, 1981). In sequence, these sites / factors were:

Traditional models of fatigue have separated the sites / factors numbered 1 to 6, and classified these as being ‘central’, whilst those numbered 4 to 8 have been classified as being ‘peripheral’. Thus, some locations are involved in both central and peripheral fatigue. Moreover, central fatigue can be located within both the central and peripheral nervous systems, being characterized by a decrease in the neural drive to the muscle. To a large extent, these early classifications of fatigue were made artificially on the basis of the experimental techniques available to study changes in muscle functional properties. In particular, the so-called twitch interpolation technique was used as a method of distinguishing fatigue originating upstream and downstream of the site of electrical stimulation (motor nerve or muscle) (Merton, 1954). The technique was first described by Denny-Brown (1928) and involves the electrical (or latterly, magnetic) stimulation of the muscle of interest, or its motor nerve. The stimulus is delivered during a voluntary contraction of the muscle, and the resulting total force depends upon the extent to which the pool of motor units accessed by the external stimulus has been activated by the voluntary effort. For example, if 100% of motor units accessible to the stimulus are activated by the voluntary drive, no additional force will be evoked by the external stimulation. In contrast, if the voluntary drive has activated only a proportion of this motor unit pool, more motor units will be recruited by the stimulation, and a ‘twitch’ of additional force will be measureable. The latter is indicative of a failure of voluntary neural drive, or ‘central fatigue’. Thus, as Merton (1954) put it, ‘If the equality [between voluntary and electrically evoked forces] still holds, then the site of fatigue must be peripheral to the point [of stimulation] of the nerve; otherwise it is central, wholly or partly’. Using electrical stimulation techniques, it has also been possible to demonstrate that well-motivated people are capable of activating muscles maximally, such that no additional force is generated electrically, compared with voluntary muscle contraction (Merton, 1954), including the respiratory muscles (Similowski et al, 1996).

Most recently, a new technique has emerged for evaluating the role of the brain in fatigue – that of transcranial magnetic stimulation. The technique involves placing a magnetic coil over the motor cortex. By harnessing electromagnetic induction, an electric current passing through a coil excites adjacent nervous tissue, generating an action potential. This method can also be used to stimulate motorneurons in the spine, as well as peripheral nerves. By careful positioning of the coil, different parts of the motor cortex can be stimulated, evoking brief contractions of specific muscles. Using these muscle activation techniques, it has become clear that feedback from contracting muscles influences the neural drive to the muscles at a number of sites; this will be considered in more detail in the section below ‘Afferent feedback and fatigue’.

Early research on fatigue mechanisms tended to focus upon the sites located at the muscle level. This was partly for pragmatic reasons, but also because Merton's muscle stimulation studies (Merton, 1954) had shown that, during maximal isometric contractions of the adductor pollicis, force could not be restored by strenuous stimulation of the muscles. Because the muscle action potential remained unchanged, the finding indicated the decline in force was due to failure within the muscle and not to failure of neuromuscular transmission. Consequently the neuromuscular junction, the influence of fuel availability and the role of accumulated metabolic ‘waste products’ became a focus of research. At one time, prolonged exercise was understood to be limited by running out of fuel, whereas high-intensity exercise was limited by running out of fuel and / or accumulation of lactic acid (McKenna & Hargreaves, 2008). In other words, fatigue was considered to be a sign of a system in crisis. However, contemporary research on fatigue recognizes not only the important contribution of the brain, but also the fact that fatigue is not a sign of catastrophic failure, but of a system making an integrated response that conserves and optimizes function. For these reasons, and for those explored below in the section ‘Afferent feedback and fatigue’, classification of fatigue as either ‘central’ or ‘peripheral’ has become increasing irrelevant.

Before considering the role of feedback from exercising muscles in fatigue processes, the potential causes of fatigue at the level of the muscle will be discussed briefly (sites 4 to 8; Bigland-Ritchie, 1981). In theory, the neuromuscular junction could present a limit to muscle activation by ‘running out’ of the neurotransmitter acetylcholine. However, there appears to be little evidence to support a role for the neuromuscular junction in fatigue (Bigland-Ritchie et al, 1982). In contrast, a reduction in sarcolemmal excitability is a potential contributor to fatigue. Failure of action potential propagation can arise for a number of reasons. For example, changes in the concentrations of sodium and potassium ions around the muscles fibres can reduce the excitability of those fibres, with a result that force is reduced (Jones et al, 2004). The next step in the process of muscle contraction is excitation–contraction coupling, which involves the release of calcium from the sarcoplasmic reticulum (SR). Calcium release, its interaction with troponin, and reuptake into the SR, are fundamental to the contraction and relaxation of muscle fibres. Hence, if release or binding of calcium to troponin is impaired, force can be reduced. Similarly, if reuptake is impaired, relaxation could be slowed. Experiments using single fibres of mouse muscle indicate that repeated bouts of high-intensity exercise can lead to a reduction in calcium release, which is associated with a loss of force (Westerblad et al, 1993). The intramuscular factors implicated in impairing calcium release are ATP, magnesium ions and inorganic phosphate, either separately or in combination; studies in patients with McArdle's syndrome suggest that pH does not contribute to impaired release of calcium (Jones et al, 2004). However, pH does influence the interaction between calcium and troponin, as do phosphate ions. Although both pH and the concentration of phosphate ions change during fatiguing exercise, the interaction between calcium and troponin is not thought to play an important role in human muscle fatigue (Jones et al, 2004). Finally, calcium removal has for many years been considered responsible for the slowing of muscle relaxation in fatigued muscle. However, there is no evidence for this association in human muscle (Jones et al, 2004).

The final stage of muscle contraction is the interaction between the contractile proteins actin and myosin, which generates muscle shortening. Studies on single fibres of fatigued mouse muscle indicate that, even when the fibres are saturated with calcium, the force generated is around 20% lower than that of the unfatigued muscle (Westerblad et al, 1993). This suggests that failure of cross-bridge function contributes to fatigue-related force deficits. Cross-bridge kinetics also influence rates of muscle shortening and relaxation and, since changes in maximum shortening velocity can be accounted for only by slowing of cross-bridge kinetics, this is a key index of cross-bridge dysfunction (Jones et al, 2004). But what factors induce such dysfunction? Because of the reversible nature of the reactions that liberate energy from ATP, it is theoretically possible that accumulation of inorganic phosphate and ADP, or depletion of ATP are responsible. However, there is currently no evidence that accumulation of inorganic phosphate and ADP, or depletion of ATP, lead to cross-bridge dysfunction (Jones et al, 2004), so other candidates must be sought. The ‘usual suspect’ is pH, but substantial detrimental effects of increases in hydrogen ion concentration ([H⁺]) appear to be limited to unphysiological ranges of muscle temperature (Jones et al, 2004). To date, there is no consensus regarding the specific metabolites that are responsible for cross-bridge dysfunction. Experiments have typically manipulated one metabolite at a time, and it is conceivable that when changes in metabolites are combined their effects become far more potent (Jones et al, 2004), but for now this remains speculation.

In summary, there appears to be no single weak link in the chain of events that produce muscle contraction, thereby triggering fatigue. In much the same way that efforts to identify a single control factor for the exercise hyperpnoea have resulted in failure, so too has the quest to find a single cause of fatigue. For such a thing to exist, it is implicit that the other links are ‘overbuilt’, which does not tend to be how evolution operates. Instead, it is more likely that all links approach ‘failure’ together, and thus all have the potential to be ‘the weakest link’. In this scheme, variations in the exercise conditions are what determine the weakest link for any given situation. This is yet another reason why reductionist models of fatigue have, and will continue to be, inadequate.

Afferent feedback, fatigue and perception of effort

Latterly, feedback signals from exercising muscles have been recognized as making an important contribution to central fatigue mechanisms, as well as to perception of effort. These afferents, their sites of action, and influences upon muscle activation are complex, and beyond the scope of this section (see Gandevia, 1998). However, one group of afferents has particular relevance in the context of respiratory muscle training, viz., group III and IV non-myelinated fibres (see Chs 3 and 4). Virtually silent at rest, these small-diameter afferents increase their discharge during muscle contraction in response to stimuli from changes in the temperature, chemical and mechanical properties of the muscle milieu. For this reason, they are often referred to as ‘metaboreceptors’, and they project to a number of sites within the central nervous system. This means they have many roles, including cardiovascular and respiratory system regulation, and effort perception (Amann et al, 2010), as well as fatigue.

Feedback from group III and IV afferents has been implicated in central fatigue mechanisms via inhibition of central motor output (Gandevia, 2001). It has been suggested (Gandevia, 2001) that afferent feedback from exercising muscles protects locomotor and respiratory muscles from catastrophic fatigue, indeed: ‘An extreme example [of central fatigue] occurs with exercise of the inspiratory muscles in which task failure can occur with minimal peripheral fatigue’ (Gandevia, 2001). Observations such as this, and more recent studies on leg muscles, have led to the hypothesis that, ‘feedback from fatiguing muscle plays an important role in the determination of central motor drive and force output, so that the development of peripheral muscle fatigue is confined to a certain level’ (Amann & Dempsey, 2008b) – in other words, that the magnitude of exercise-induced muscle fatigue is a regulated variable (Amann & Dempsey, 2008a).

The importance of group III and IV afferent feedback in regulating integrated exercise responses was illustrated recently by an elegant study in which a cycle time trial was undertaken with and without the selective μ-opioid receptor agonist fentanyl, an agent affecting only afferent fibres (Amann et al, 2009). During a self-paced 5 km (5000 m) time trial, intrathecal fentanyl was associated with greater quadriceps fatigue, a higher central motor output and greater perceived exertion compared with placebo. A higher power output in the first half of the fentanyl time trial was offset by a lower power output in the second, resulting in no change in performance time. However, compared with placebo the decline in quadriceps twitch force was greater with fentanyl (45.6% vs 33.1%) and was associated with ambulatory problems post-exercise. The authors suggest their data ‘emphasize the critical role of locomotor muscle afferents in determining the subject's choice of the “optimal” exercise intensity that will allow for maximal performance while preserving a certain level of locomotor muscle “functional reserve” at end-exercise’ (Amann et al, 2009). The specific contribution of respiratory muscle groups III and IV afferents to central fatigue during whole-body exercise awaits investigation. Given the importance of protecting diaphragm function, it is reasonable to speculate that the inhibitory feedback from inspiratory muscle afferents during exercise influences both respiratory and locomotor central motor output. As we will discover in Chapters 3 and 4, feedback from inspiratory muscle metaboreceptors makes an important contribution to cardiovascular control, regulation of limb blood flow and hence to factors that affect development of muscle fatigue (McConnell & Lomax, 2006; Romer et al, 2006).

Task failure and task dependency

An important distinction that has been made within the past two decades is between the concepts of fatigue and task failure (Barry & Enoka, 2007; Astrand et al, 2003). Typical experimental designs used to elucidate fatigue are to quantify: (1) the decline in maximum contraction force (voluntary or evoked electrically) during a bout of fatiguing contractions, and (2) the decline in force or power immediately after the fatiguing contractions (Enoka & Duchateau, 2008). These experiments reveal that fatigue is an evolving process that may or may not lead to task failure and cessation of exercise (Bigland-Ritchie & Woods, 1984). In their 2007 update of Enoka & Stuart's 1992 review, Barry & Enoka (2007) acknowledge that ‘The most common definition of fatigue in the past decade is that it corresponds to an exercise-induced reduction in the ability of the muscle to produce force or power, whether or not the task can be sustained’. For this reason, the notion of fatiguing contractions is an important one, since is describes an intensity domain in which fatigue begins early in the task, but does not necessarily lead to an inability to sustain the task, or indeed to any measurable failure in, say, maximum voluntary contraction force at its cessation. This is an important concept, since the lack of residual respiratory muscle fatigue post-exercise (e.g., an impairment of diaphragm function) is often cited as an argument for the futility of inspiratory muscle training (Polkey & Moxham, 2004). As has been explained above, failure of muscle activation can occur at any number of sites, not just the contractile machinery.

Furthermore, just as any definition of fatigue must accommodate multiple factors, the process of fatigue itself is multifactorial and, ultimately, task dependent. Research has now shown that the factors precipitating fatigue are specific to the task, and include participant motivation, pattern of muscle activation, intensity and duration of activity, and continuous or intermittent activity (Barry & Enoka, 2007). For example, studies comparing the responses of older and younger men to two types of muscle contractions showed that older men were more fatigable during dynamic contractions, whilst younger men were more fatigable during isometric contractions (Barry & Enoka, 2007). The explanation for these differences resides in an understanding that there is no single cause of fatigue. As was described above, several linked processes contribute to muscle contraction, and impairment of any one process, or any combination of processes, can result in fatigue. Different tasks impair different physiological processes, thereby determining the task specificity of fatigue. For maximal-intensity tasks, the development of fatigue is linked closely to the decline in performance, and task failure. In contrast, for sub-maximal intensity tasks, fatigue may develop but might not lead to task failure. Because an activity such as breathing generally requires sub-maximal intensity work by the respiratory pump muscles, contractile fatigue of these muscles may not be the cause of task failure, even when the task involves breathing against a load.

Indeed, task failure may not be the result of fatigue of the principal muscles involved in the task (Enoka & Duchateau, 2008). For example, when human beings inhale against inspiratory loads ranging between 75% and 90% of the maximal strength of their inspiratory muscles, all reach task failure within 20 minutes (McKenzie et al, 1997). However, none exhibited inspiratory muscle fatigue; instead, task failure was associated with hypercapnia and dyspnoea. Even in similar studies, where the work history of the inspiratory muscles has been manipulated to induce prior fatigue, task failure was not related to the severity of inspiratory muscle fatigue (Rohrbach et al, 2003). Rather, task failure appeared to be related to hypercapnia and / or arterial oxygen desaturation.

Because of the seeming futility of identifying any unifying cause(s) of fatigue, research has shifted to focus upon task failure, i.e., the duration for which a task can be sustained. This is not only pragmatic scientifically, but also in terms of the relevance of the findings to everyday life, since it is the failure to sustain the task that impacts upon the individual, not the mechanism(s) of fatigue; individuals can seemingly continue to function in the presence of fatigue, and it may only be when the point of task failure is approached that performance of the task is impaired.

An enlightening model used to elucidate the mechanisms contributing to task failure of limb muscles has been to compare the responses to two tasks of differing difficulty (Hunter et al, 2004). In one task the limb is fixed, and a predetermined isometric force must be sustained for as long as possible. In the second task, an inertial load (requiring the same muscle force as the first task) must be maintained in a specified position for as long as possible. The latter is the more difficult task, which is reflected in the shorter time to task failure (Hunter et al, 2004). By comparing performance of these two tasks it is possible to identify the adjustments that limit the duration of the more difficult task. These studies have revealed that the neural strategies utilized to deliver the two tasks differ. In the more difficult task, heightened activation of the muscle stretch reflex from the unsupported limb appears to lead to earlier recruitment of the motor unit pool and more rapid termination of the task (Maluf & Enoka, 2005). The additional challenge generated by postural control of the limb has also been studied in the context of the role of synergistic and accessory muscle contributions to the task (Rudroff et al, 2007). Unsurprisingly, tasks that required an accessory muscle contribution were briefer than those that did not.

These data provide empirical confirmation of the anecdotal observation that lifting free weights is more challenging than lifting ‘machine’ weights (where there is typically only one plane of movement). Confirmation of the highly task-dependent nature of fatigue supports an argument for the development of ‘functional’ tests of muscle fatigue, as well as for the application of functional principles to muscle training, especially where the objective is to improve performance in activities of daily living (Maluf & Enoka, 2005).

As will be described in Chapter 3, the respiratory muscles are engaged in a number of non-respiratory tasks related to postural control and stabilization of the trunk. Based upon knowledge gained from limb muscles (Maluf & Enoka, 2005), it is reasonable to postulate that a respiratory task such as sustaining exercise hyperpnoea will be more challenging, and potentially limiting, under conditions where these muscles are also engaged in non-respiratory tasks.

Summary

The preceding section might seem to create more questions than answers, but fatigue is an extremely complex phenomenon that contributes to exercise limitation. Fatigue is a process with no single cause, and which may or may not result in task failure. Fatigue also displays plasticity, being influenced by changes in an individual's characteristics, such as the presence of disease or improvements in the neuromuscular system brought about by training. This plasticity may create weak links in the ‘fatigue chain’, just as it may strengthen them, thereby changing the balance of factors contributing to exercise limitation.

1. Alveolar ventilation: Delivery of atmospheric air to the alveoli (breathing)

2. Pulmonary diffusion: Transfer of O₂ from the alveoli to the capillary blood

3. Transport by the blood I: Loading of O₂ at the lungs

4. Transport by the blood II: Delivery of O₂ to the muscle cells via the circulation

5. Tissue diffusion: Transfer of O₂ from the muscle capillary blood to the muscle cells.

Maximal oxygen uptake

In the previous section we considered how is the rate-limiting step in the transport of O₂ to exercising muscles. In this section the ability of the body to utilize O₂ to undertake external work will be discussed.

In the previous section the analogy of a haulage company supplying goods to stores was used to illustrate the role of in O₂ transport. In an extension to that analogy, we can think of O₂ uptake (O₂) by the muscles as being akin to the sales of the goods, which are a function of the rate of delivery and the customer demand; both are required in order to achieve sales. In the same way, muscle O₂ is a function of blood flow and O₂ utilization. The utilization of O₂ is the amount of O₂ extracted from the blood as it passes through the tissue, i.e., the arterial to mixed venous O₂ difference (a–O₂). Thus, the O₂ of a muscle is given by the equation:

O₂ =  × a–O₂

During exercise, not only does blood flow to a muscle increase, but the extraction of oxygen from the blood is also enhanced, widening the a–O₂.

The O₂ of the entire body can be measured by using the a–O₂ difference measured at the lungs. Typically, this gradient is around 5 ml at rest, but can be three times this value during heavy exercise. The change is generated by an increased extraction of O₂ by the muscles, which produces a reduction in mixed venous O₂ content and a wider a–O₂ difference. However, measuring and pulmonary a– O₂ difference is a highly invasive method of assessing total body O₂; fortunately, it can also be estimated by subtracting the amount of oxygen exhaled from the amount inhaled at the mouth.

The maximal oxygen uptake (O_2max; also called maximal oxygen consumption or aerobic capacity) is an index that combines both the maximal ability to transport and to utilize O₂. It can be defined for an exercising muscle group, but is more frequently defined for the whole body during exercise by measuring O₂ at the mouth. During exercise at sea level requiring the involvement of > 30% of the total muscle mass, O_2max is limited by , and not by the ability of the muscles to consume O₂ (Gonzalez-Alonso & Calbet, 2003). For this reason, O_2max is used as an index of cardiovascular function, as well as of ‘aerobic fitness’.

Typically, O_2max is estimated by undertaking an incremental exercise test to the limit of tolerance. An example of the O₂ response to such a test is provided in the bottom right panel of Figure 2.2. The gold standard criterion for a test that is limited by physiological factors is a plateau of O₂, despite an increase in the external work done. If this plateau is not observable, a number of secondary criteria can be used to imply maximality. These include, either individually or in combination, the following (Poole et al, 2008):

However, use of these indirect criteria has been shown to underestimate O_2max by as much as 27% (Poole et al, 2008). Accordingly, prudence is advised, and the term O₂ peak (O_2peak) should be used in order to distinguish the value from a true O_2max that was limited by central cardiovascular function (). The term O_2peak is also used in situations where none of these criteria have been met, as will be the case in many patients who are symptom limited by factors such as dyspnoea.

The ability to sustain high levels of external work without becoming fatigued is very closely related to one's O_2max. Hence, endurance athletes tend to have high values, but so too do very large people with a large muscle mass. Accordingly, O_2max is often expressed as a relative value by dividing the value expressed in ml·min^− 1 by body mass in kilograms to give relative O_2max in ml·min^− 1.kg^− 1. Body mass also needs to be borne in mind when considering weight-bearing and non-weight-bearing exercise. For example, being heavy is no disadvantage when cycling a stationary ergometer, but is a considerable disadvantage during walking and running. Accordingly, compared with an overweight individual with a low relative O_2max, a slight individual with a high relative O_2max may have a lower ability to sustain a moderate power output on a cycle ergometer, but a much greater ability to sustain ambulation at a moderate speed.

Furthermore, for athletes, having a high relative O_2max does not necessarily imply that they will be a good marathon runner. Although, as a population, marathon runners all have a high relative O_2max, within this population, performance is not predicted by O_2max. In other words, two athletes with the same relative O_2max can have very different marathon running times. This is because of the influence of two other factors upon performance: (1) the lactate threshold (LaT) and (2) exercise economy. Each will be considered below.

The response of O_2max to training will be considered in the section ‘Training adaptations’, below.

Lactate threshold

The term lactate threshold (LaT) is slightly misleading, because it implies that it corresponds to an exercise intensity at which anaerobic metabolism is switched on abruptly. This is not the case, because anaerobic metabolism takes place constantly. Even at very low intensities of exercise, inhomogeneity of blood flow distribution within muscles means that some muscle fibres and groups of fibres receive inadequate blood flow, resulting in reliance upon anaerobic metabolic pathways. The production of lactic acid (La; also known as lactate) therefore takes place constantly, but La is also metabolized constantly, in a continuous cycle of production and breakdown. So long as there is sufficient spare aerobic capacity to metabolize La, the concentration in the blood may be elevated slightly, but there is no accumulation of La. However, when the intensity of exercise exceeds the capacity to break down La, it will continue to accumulate in the tissues and blood until exercise is terminated. Because of the detrimental influence of La upon pH and muscle function, exercise above the LaT is non-sustainable and the inevitable end point is exercise intolerance. The LaT should be thought of as an intensity domain during exercise that results in an elevated concentration of La in the blood ([La]); further increases in exercise intensity above this level result in a progressive increase in the [La] and eventual exercise intolerance.

The impact of the LaT upon exercise tolerance is therefore to determine the maximum exercise intensity at which exercise is sustainable for prolonged periods of time. Typically, the LaT occurs at around 50–60% of O_2max. However, in highly trained endurance athletes it may be as high at 90% O_2max. This is why athletes with the same O_2max can have very different marathon performances; the athlete whose LaT occurs at the highest percentage of his or her O_2max can sustain a higher running speed over the course of the marathon.

The LaT is highly responsive to training, which will be considered in ‘Training adaptations’ (below).

Exercise economy

The final piece in the performance jigsaw is exercise economy, i.e., the oxygen cost of exercise. At the very top of elite sport, where O_2max and LaT have been optimized, economy appears to be the factor that differentiates world champions from ‘also rans’ (Foster & Lucia, 2007).

As well as being determined by external factors such as the effects of aerodynamic drag, movement economy is determined by a number of intrinsic factors (Saunders et al, 2004):

Exercise economy is responsive to training, but improvements are difficult to obtain, and scientific evidence to support particular training interventions is limited (Midgley et al, 2007). Accordingly, this aspect of performance will not be considered any further. However, it should be clear that, in patients with obvious difficulties with ambulation, interventions that improve exercise economy also improve exercise tolerance.

Cardiovascular training adaptations

Oxygen delivery to the exercising muscles can be increased by improving the function of both the heart and the circulatory system. From the preceding sections it will be apparent that the limitations imposed by upon O₂ transport make the pumping capacity of the heart a prime candidate for improvement. Since the heart's main function is as a pump, the specificity principle dictates that overload must tax the heart's ability to eject a bolus of blood into the circulation, i.e., improving SV. The determinants of SV are the volume of blood returning to the heart (venous return), the ability of the left ventricle to accommodate blood and the efficiency with which the ventricle is able to eject the blood it contains. In practice this means undertaking whole-body activities that elevate heart rate; however, just as the resistance training of skeletal muscles requires the right combination of load and duration (repetitions), so too does training the myocardium. Typically, for very-high-intensity exercise, the duration of the training stimulus should be ≥ 90 seconds, whilst for sub-maximal exercise it should be ≥ 10 minutes (Jones & Poole, 2009). These types of ‘aerobic’ activities also deliver a training stimulus to the rest of the circulatory system, and to the exercising muscles. Improving circulatory and muscle function will improve O_2max and LaT, with O_2max typically having the potential to increase by around 20% in a previously sedentary individual. However, the magnitude of this increase can be greater in people with extremely low baseline function, and also depends upon the intensity and duration of the training stimulus, as well as the frequency and duration of the training programme. Responsiveness to training also varies enormously between individuals owing to genetic predisposition. Just as training can ‘give’ O_2max, inactivity can ‘taketh away’, with a loss of O_2max at the rate of around 1% per day over a period of up to 30 days of bed rest (Convertino, 1997).

The specific adaptations that result in the functional outcome of an improvement in O_2max and LaT fall into three main categories: myocardial, circulatory and muscle adaptations.

Respiratory training adaptations

In light of the huge capacity of the cardiovascular system to adapt to training, one might expect the lungs to exhibit a similar degree of plasticity. To most people's surprise, the lungs show no training response. Unlikely though it seems, training does not increase lung volumes, improve lung function, or enhance the ability of the lungs to transfer oxygen to the blood, even in athletes who have trained for many years (Wagner, 2005).

Notwithstanding this inability to adapt to training, the observation that the lung function of athletes such as swimmers and rowers is superior to that of their non-athletic contemporaries has led to speculation that physical training, especially during childhood and adolescence, may enhance the development of the lungs (Armour et al, 1993). However, one cannot exclude the possibility that, for some sports, having large lungs may provide an advantage that leads to success. Hence only competitors with larger than normal lungs succeed and remain to compete in their chosen sport as adults.

Notwithstanding the intransigence of the lungs per se to adapt to training, the musculature of the respiratory pump (Powers & Criswell, 1996) and upper airway (Vincent et al, 2002) has been shown to respond to endurance training. There is also evidence that endurance training raises the intensity of inspiratory muscle work required to activate the inspiratory muscle metaboreflex (Callegaro et al, 2011). This reflex is know to impair O₂ delivery to exercising locomotor muscles (Harms et al, 1997) and to exacerbate fatigue (Romer et al, 2006).

Whole-body exercise training also results in higher peak _E during exercise, as well as a lower ventilatory equivalent for oxygen (_E / O₂), i.e., a reduced breathing requirement for exercise. The latter results from an increase in V_T, and a corresponding improvement in the dead space to tidal volume ratio (V_D / V_T), which increases alveolar ventilation (V_A), lessening the _E requirement. As was discussed above (see ‘Cardiorespiratory limitation of exercise tolerance’), an improved respiratory-pumping capacity does not enhance blood oxygenation, but it does enhance the ability to make a respiratory compensation for a metabolic acidosis.

The response of the respiratory musculature to specific resistance training and the associated functional benefits are described in detail in Chapter 4.

Exercise modality

Overload of the cardiorespiratory system can be achieved using a wide variety of exercise modalities. Traditional activities include, brisk walking, running, cycling, swimming, rowing, cross-country skiing, and even dancing. In a health-club setting, machines have been created that provide the involvement of large muscles mass, with some of the discomforts and injury risks of traditional activities, including stair climbers, elliptical walkers, arm crank ergometers, etc. When selecting an exercise modality for training, a large number of highly personal factors come into play, e.g., personal preference, orthopaedic limitation, skill, personal finances, etc. In practical terms, the optimal training mode is the one that the individual is most likely to engage with in accordance with the requirements of the training regimen.

However, the specificity principle limits the extent to which cardiorespiratory improvements transfer between different exercise modalities (Millet et al, 2009). In other words, a 15% increase in O_2max achieved through cycle training will not necessarily result in the same improvement in O_2max during running. The reasons for this are not fully understood, but probably arise because of the specificity of the peripheral adaptations to muscle structure and function, as well as biomechanics. Notwithstanding these limitations, many athletes uses a range of exercise modalities, so-called ‘cross training’, as a means of lessening boredom, and of reducing the risk of overuse injuries. Cross training can also enhance adherence to training, especially at a recreational level.

With the specificity principle in mind, it is also important to consider how exercise modality impacts upon the broad range of training benefits. Whilst O_2max might be one of the main physiological outcomes that a particular training programme targets, maximizing O_2max is unlikely to be the goal from the perspective of the individual undertaking the training. For example, an amateur competitive runner is more likely to be focussed on, say improving their 10 km time. Although O_2max improvement may contribute to the achievement of personal goals, it is not an end in itself particularly, as the limitation to the 10 km performance may not reside in O_2max but in the running speed corresponding to the LaT. With goals and specificity in mind, if one is training to increase 10 km running performance then this is best achieved through the practice of running, and using a training regimen that overloads both O_2max and LaT.

Before closing this section, there is one final aspect of specificity to consider, i.e., the role of the trunk musculature in specific exercise modalities (see also Ch. 3, ‘Non-respiratory functions of the respiratory muscles’). A striking phenomenon, particularly in non-athletes, is the greater intensity of dyspnoea at equivalent O₂ during walking / running than during cycling. The mechanism underpinning this is the involvement of the respiratory musculature in postural control during running – a challenge that is not present during cycling, especially on a stationary ergometer. In other words, the respiratory muscles are required to multi-task during running, which increases respiratory muscle work and exacerbates dyspnoea. The implications of this are three-fold: (1) if training overload is limited by dyspnoea during walking / running, then an alternative modality (e.g., cycling) might enhance the overall aerobic training response, (2) if reducing dyspnoea during activities of daily living is a goal, then using cycling as a means of training does not deliver a sufficiently specific training overload, because it does not address the postural role of the trunk muscles during exercise, and (3) supplementing or preceding the aerobic training with specific respiratory muscle and postural training may enhance the final training outcome by reducing limitations arising from dyspnoea.

Aerobic capacity (O_2max)

The ability of the cardiovascular system to deliver oxygenated blood to the exercising muscles is the weakest link in the O₂ delivery system determining aerobic capacity, i.e., O_2max. Improvement of O_2max is therefore underpinned principally by the improvement of O₂ delivery by the cardiovascular system. Accordingly, training interventions that are intended to increase O_2max must overload the cardiovascular contribution to O₂ delivery. Improvement in O_2max has become synonymous with the concept of ‘endurance’ training, i.e., undertaking prolonged, moderate-intensity exercise. However, this traditional view is changing and there is evidence supporting alternative training to enhance O_2max.

In common with many interventions that influence biological processes, exercise possesses a dose–response relationship. Accordingly, when devising a training regimen there are a number of key factors that make up the exercise ‘prescription’, and the thresholds for each differ according to the starting level of O_2max:

There is no ‘magic bullet’ training regimen for increasing O_2max, but Table 2.2 attempts to provide some approximate, evidence-based guidance. As well as bearing in mind the enormous heterogeneity of responsiveness to training, the necessity to vary and progress the stimulus must also be borne in mind. In addition, the table provides minimum thresholds; optimized benefits are achieved by maximizing training intensity. For example, in previously sedentary men, training at 80% O_2max three times per week elicited a greater increase in O_2max than training at 60% O_2max, at equivalent caloric expenditure per training session (400 kcal).

The progression of training is essential, as improvements in absolute O_2max will render a given percentage of O_2max relatively less intense. Any of the three aforementioned components of the training prescription can be varied in order to maintain overload. Current guidelines make no specific recommendations, but common sense suggests that a combination of all three components is required (Garber et al, 2011).

Lactate threshold

The intensity of exercise corresponding to the LaT is determined primarily by the oxidative capacity of the active muscle mass (Ivy et al, 1980). As was discussed above, the LaT represents the intensity at which the production of lactic acid exceeds its breakdown. Endurance training appears to increase the intensity of exercise corresponding to the LaT by enhancing the ability to break down lactic acid (Donovan & Brooks, 1983). Thus exercise regimens that overload the lactate clearance mechanisms are required in order to elicit improvement in LaT. A typical training session to achieve this goal will be ~ 20 minutes in duration at an intensity of ~ 90% O_2max. However, there are a variety of methods that can be used to enhance LaT, including interval training at maximal (100% O_2max) and supramaximal (130% O_2max) intensities, in bouts that are sustained for ~ 3 minutes and 30 seconds, respectively (Esfarjani & Laursen, 2007). These training regimens also improve O_2max, with the largest increase in both parameters (~ 10%) observed after interval training at 100% O_2max for ~ 3 minutes (8 bouts per session, two times per week) (Esfarjani & Laursen, 2007).

High-intensity interval training is not only a very time-efficient method of enhancing both LaT and O_2max, it may also be better tolerated in individuals in whom the escalating intensity of exercise-related symptoms can limit the ability to undertake continuous exercise, e.g., dyspnoeic patients. Notwithstanding this, high-intensity training may also be contraindicated for certain individuals, especially those with cardiovascular disease. Accordingly, the design of a training regimen needs to be made on the basis of the clinical profile of the individual involved.

Amann, M., Dempsey, J.A. The concept of peripheral locomotor muscle fatigue as a regulated variable. J. Physiol. 2008;586:2029–2030.

Amann, M., Dempsey, J.A. Locomotor muscle fatigue modifies central motor drive in healthy humans and imposes a limitation to exercise performance. J. Physiol. 2008;586:161–173.

Amann, M., Proctor, L.T., Sebranek, J.J., et al. Opioid-mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans. J. Physiol. 2009;587:271–283.

Amann, M., Blain, G.M., Proctor, L.T., et al. Group III and IV muscle afferents contribute to ventilatory and cardiovascular response to rhythmic exercise in humans. J. Appl. Physiol. 2010;109:966–976.

Armour, J., Donnelly, P.M., Bye, P.T. The large lungs of elite swimmers: an increased alveolar number? Eur. Respir. J. 1993;6(2):237–247.

Astrand, P.O., Rodahl, K., Stromme, S. Textbook of work physiology: Physiological bases of exercise, fourth ed. Champaign, IL: Human Kinetics; 2003. [p. 185].

Barry, B.K., Enoka, R.M. The neurobiology of muscle fatigue: 15 years later. Integrative and Comparative Biology. 2007;47:465–473.

Bigland-Ritchie, B. EMG and fatigue of human voluntary and stimulated contractions. In: Porter R., Whelan J., eds. Human muscle fatigue: physiological mechanisms. London: Pitman Medical; 1981:130–156.

Bigland-Ritchie, B., Woods, J.J. Changes in muscle contractile properties and neural control during human muscular fatigue. Muscle Nerve. 1984;7:691–699.

Bigland-Ritchie, B., Kukulka, C.G., Lippold, O.C., et al. The absence of neuromuscular transmission failure in sustained maximal voluntary contractions. J. Physiol. 1982;330:265–278.

Cady, E.B., Elshove, H., Jones, D.A., et al. The metabolic causes of slow relaxation in fatigued human skeletal muscle. J. Physiol. 1989;418:327–337.

Callegaro, C.C., Ribeiro, J.P., Tan, C.O., et al. Attenuated inspiratory muscle metaboreflex in endurance-trained individuals. Respir. Physiol. Neurobiol. 2011;177:24–29.

Convertino, V.A. Cardiovascular consequences of bed rest: effect on maximal oxygen uptake. Med. Sci. Sports Exerc. 1997;29:191–196.

Davies, C.T., Sargeant, A.J. Physiological responses to one- and two-leg exercise breathing air and 45 percent oxygen. J. Appl. Physiol. 1974;36:142–148.

Denny-Brown, D.E. On inhibition as a reflex accompaniment of the tendon jerk and of other forms of active muscular response. Proc. R. Soc. Lond. B Biol. Sci. 1928;103:321–326.

Donovan, C.M., Brooks, G.A. Endurance training affects lactate clearance, not lactate production. Am. J. Physiol. 1983;244:E83–E92.

El-Sayed, M.S., Ali, N., El-Sayed Ali, Z. Haemorheology in exercise and training. Sports Med. 2005;35:649–670.

Enoka, R.M., Duchateau, J. Muscle fatigue: what, why and how it influences muscle function. J. Physiol. 2008;586:11–23.

Enoka, R.M., Stuart, D.G. Neurobiology of muscle fatigue. J. Appl. Physiol. 1992;72:1631–1648.

Esfarjani, F., Laursen, P.B. Manipulating high-intensity interval training: effects on VO2max, the lactate threshold and 3000 m running performance in moderately trained males. J. Sci. Med. Sport. 2007;10:27–35.

Foster, C., Lucia, A. Running economy: the forgotten factor in elite performance. Sports Med. 2007;37:316–319.

Gandevia, S.C. Neural control in human muscle fatigue: changes in muscle afferents, motoneurones and motor cortical drive [corrected]. Acta Physiol. Scand. 1998;162:275–283.

Gandevia, S.C. Spinal and supraspinal factors in human muscle fatigue. Physiol. Rev. 2001;81:1725–1789.

Garber, C.E., Blissmer, B., Deschenes, M.R., et al, American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med. Sci. Sports Exerc. 2011;43:1334–1359.

Gillen, C.M., Lee, R., Mack, G.W., et al. Plasma volume expansion in humans after a single intense exercise protocol. J. Appl. Physiol. 1991;71:1914–1920.

Gonzalez-Alonso, J. Human thermoregulation and the cardiovascular system. Exp. Physiol. 2012;97:340–346.

Gonzalez-Alonso, J., Calbet, J.A. Reductions in systemic and skeletal muscle blood flow and oxygen delivery limit maximal aerobic capacity in humans. Circulation. 2003;107:824–830.

Hamilton, A.L., Killian, K.J., Summers, E., et al. Quantification of intensity of sensations during muscular work by normal subjects. J. Appl. Physiol. 1996;81:1156–1161.

Harms, C.A., Dempsey, J.A. Cardiovascular consequences of exercise hyperpnea. Exerc. Sport Sci. Rev. 1999;27:37–62.

Harms, C.A., Babcock, M.A., McClaran, S.R., et al. Respiratory muscle work compromises leg blood flow during maximal exercise. J. Appl. Physiol. 1997;82:1573–1583.

Harms, C.A., Wetter, T.J., McClaran, S.R., et al. Effects of respiratory muscle work on cardiac output and its distribution during maximal exercise. J. Appl. Physiol. 1998;85:609–618.

Harms, C.A., Wetter, T.J., St Croix, C.M., et al. Effects of respiratory muscle work on exercise performance. J. Appl. Physiol. 2000;89:131–138.

Haskell, W.L., Lee, I.M., Pate, R.R., et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med. Sci. Sports Exerc. 2007;39:1423–1434.

Holloszy, J.O., Booth, F.W. Biochemical adaptations to endurance exercise in muscle. Annu. Rev. Physiol. 1976;38:273–291.

Hunter, S.K., Duchateau, J., Enoka, R.M. Muscle fatigue and the mechanisms of task failure. Exerc. Sport Sci. Rev. 2004;32:44–49.

Hussain, S.N.A., Comtois, A.S. Regulation of skeletal muscle blood flow during exercise. In: Hamid Q., Shannon J., Martin J., eds. Physiologic basis of respiratory disease. Hamilton, ONT: Decker; 2005:555–566.

Ivy, J.L., Withers, R.T., Van Handel, P.J., et al. Muscle respiratory capacity and fiber type as determinants of the lactate threshold. J. Appl. Physiol. 1980;48:523–527.

Jones, A.M., Poole, D.C. Physiological demands of endurance exercise. In: Maughan R.J., ed. Olympic textbook of science in sport. Oxford: Blackwell; 2009:43–55.

Jones, D.A., de Haan, A., Round, J.M. Skeletal muscle: from molecules to muscles. London: Churchill Livingstone; 2004.

Laughlin, M.H., Roseguini, B. Mechanisms for exercise training-induced increases in skeletal muscle blood flow capacity: differences with interval sprint training versus aerobic endurance training. J. Physiol. Pharmacol. 2008;59(Suppl. 7):71–88.

Levick, R.J. An introduction to cardiovascular physiology. London: Hodder Arnold; 2009.

Maluf, K.S., Enoka, R.M. Task failure during fatiguing contractions performed by humans. J. Appl. Physiol. 2005;99:389–396.

McConnell, A.K. Breathe strong, perform better. Champaign, IL: Human Kinetics Publishers; 2011.

McConnell, A.K., Lomax, M. The influence of inspiratory muscle work history and specific inspiratory muscle training upon human limb muscle fatigue. J. Physiol. 2006;577:445–457.

McKenna, M.J., Hargreaves, M. Resolving fatigue mechanisms determining exercise performance: integrative physiology at its finest!. J. Appl. Physiol. 2008;104:286–287.

McKenzie, D.K., Allen, G.M., Butler, J.E., et al. Task failure with lack of diaphragm fatigue during inspiratory resistive loading in human subjects. J. Appl. Physiol. 1997;82:2011–2019.

Merton, P.A. Voluntary strength and fatigue. J. Physiol. 1954;123:553–564.

Meyer, T., Auracher, M., Heeg, K., et al. Does cumulating endurance training at the weekends impair training effectiveness? Eur. J. Cardiovasc. Prev. Rehabil. 2006;13:578–584.

Midgley, A.W., McNaughton, L.R., Wilkinson, M. Is there an optimal training intensity for enhancing the maximal oxygen uptake of distance runners? Empirical research findings, current opinions, physiological rationale and practical recommendations. Sports Med. 2006;36:117–132.

Midgley, A.W., McNaughton, L.R., Jones, A.M. Training to enhance the physiological determinants of long-distance running performance: can valid recommendations be given to runners and coaches based on current scientific knowledge? Sports Med. 2007;37:857–880.

Millet, G.P., Vleck, V.E., Bentley, D.J. Physiological differences between cycling and running: lessons from triathletes. Sports Med. 2009;39:179–206.

Polkey, M.I., Moxham, J. Improvement in volitional tests of muscle function alone may not be adequate evidence that inspiratory muscle training is effective. Eur. Respir. J. 2004;23:5–6.

Poole, D.C., Wilkerson, D.P., Jones, A.M. Validity of criteria for establishing maximal O2 uptake during ramp exercise tests. Eur. J. Appl. Physiol. 2008;102:403–410.

Powers, S.K., Criswell, D. Adaptive strategies of respiratory muscles in response to endurance exercise. Med. Sci. Sports Exerc. 1996;28:1115–1122.

Priban, I.P., Fincham, W.F. Self-adaptive control and respiratory system. Nature. 1965;208:339–343.

Rohrbach, M., Perret, C., Kayser, B., et al. Task failure from inspiratory resistive loaded breathing: a role for inspiratory muscle fatigue? Eur. J. Appl. Physiol. 2003;90:405–410.

Romer, L.M., Polkey, M.I. Exercise-induced respiratory muscle fatigue: implications for performance. J. Appl. Physiol. 2008;104:879–888.

Romer, L.M., Lovering, A.T., Haverkamp, H.C., et al. Effect of inspiratory muscle work on peripheral fatigue of locomotor muscles in healthy humans. J. Physiol. 2006;571:425–439.

Rudroff, T., Barry, B.K., Stone, A.L., et al. Accessory muscle activity contributes to the variation in time to task failure for different arm postures and loads. J. Appl. Physiol. 2007;102:1000–1006.

Saunders, P.U., Pyne, D.B., Telford, R.D., et al. Factors affecting running economy in trained distance runners. Sports Med. 2004;34:465–485.

Scharhag, J., Schneider, G., Urhausen, A., et al. Athlete's heart: right and left ventricular mass and function in male endurance athletes and untrained individuals determined by magnetic resonance imaging. J. Am. Coll. Cardiol. 2002;40:1856–1863.

Similowski, T., Duguet, A., Straus, C., et al. Assessment of the voluntary activation of the diaphragm using cervical and cortical magnetic stimulation. Eur. Respir. J. 1996;9:1224–1231.

Sinoway, L., Prophet, S. Skeletal muscle metaboreceptor stimulation opposes peak metabolic vasodilation in humans. Circ. Res. 1990;66:1576–1584.

Stallknecht, B., Vissing, J., Galbo, H. Lactate production and clearance in exercise. Effects of training. A mini-review. Scand. J. Med. Sci. Sports. 1998;8:127–131.

Swain, D.P. Moderate or vigorous intensity exercise: which is better for improving aerobic fitness? Prev. Cardiol. 2005;8:55–58.

Vincent, H.K., Shanely, R.A., Stewart, D.J., et al. Adaptation of upper airway muscles to chronic endurance exercise. Am. J. Respir. Crit. Care Med. 2002;166:287–293.

Wagner, P.D. Why doesn't exercise grow the lungs when other factors do? Exerc. Sport Sci. Rev. 2005;33(1):3–8.

Westerblad, H., Duty, S., Allen, D.G. Intracellular calcium concentration during low-frequency fatigue in isolated single fibers of mouse skeletal muscle. J. Appl. Physiol. 1993;75:382–388.

Williams C., Ratel S., eds. Human muscle fatigue. London: Routledge, 2009.

Wilmore, J.H., Stanforth, P.R., Gagnon, J., et al. Cardiac output and stroke volume changes with endurance training: the HERITAGE Family Study. Med. Sci. Sports Exerc. 2001;33:99–106.

Wilmore, J.H., Stanforth, P.R., Gagnon, J., et al. Heart rate and blood pressure changes with endurance training: the HERITAGE Family Study. Med. Sci. Sports Exerc. 2001;33:107–116.