More modern attempts to understand the factors that determine fatigue and superior athletic performance can be traced to European studies beginning in the late nineteenth century. An influential book (Mosso, 1915
) written by Italian physiologist A. Mosso, Professor of Physiology at the University of Turin was one of the first to consider the biological basis for the fatigue that develops during exercise. From his observations of a range of natural performances by animals and birds and of experimental muscle fatigue in human subjects, Mosso concluded that: “In raising a weight we must take account of two factors, both susceptible to fatigue. The first is of central origin and purely nervous in character – namely, the will; the second is peripheral, and is the chemical force which is transformed into mechanical work” (pp. 152–153). He made a number of other observations that were prescient including: “On an examination of what takes place in fatigue, two series of phenomena demand our attention. The first is the diminution of the muscular force. The second is fatigue as a sensation” (p. 154); and “If we regard the brain and the muscles as two telegraph offices, we can understand that the nerves which join them do not suffer from fatigue. But the central or psychical station may influence the peripheral or muscular station, even if the latter is not doing work, seeing that both brain and muscles are irrigated by the blood” (p. 281). He also understood that fatigue that “at first sight might appear an imperfection of our body, is on the contrary one of its most marvelous perfections. The fatigue increasing more rapidly than the amount of work done saves us from the injury which lesser sensibility would involve for the organism” (p. 156). He realized too that the brain is unique as it is the only organ protected from the effects of starvation: “If the brain is the organ in which the most active change of material takes place, how can one explain the fact that it does not diminish in weight when all the rest of the body is wasting?” (p. 282). But he is best remembered for being one of the first to propose that “nervous fatigue is the preponderating phenomenon, and muscular fatigue also is at bottom an exhaustion of the nervous system” (Bainbridge, 1919
, p. 177).
It has taken studies of “fatigue” more than a century (Di Giulio et al., 2006
) to rediscover what Mosso believed to be obvious – that both the brain (Marcora et al., 2009
) and the skeletal muscles (Amann et al., 2006
; Amann and Dempsey, 2008
) alter their function during exercise; that the change in skeletal muscle function is characterized by a slowing of the force and speed of contraction (Jones et al., 2009
); and that fatigue is principally an emotion (St Clair Gibson et al., 2003
), part of a complex regulation (Noakes et al., 2004
; Noakes, 2011b
), the goal of which is to protect the body from harm part. So fatigue is indeed one of the human body’s “most marvelous perfections.”
Interestingly Mosso’s ideas did not gain immediate purchase in the exercise sciences but lay dormant until rediscovered more recently (Di Giulio et al., 2006
). Instead they were supplanted after 1923 by a different and more simplistic interpretation promoted by English Nobel Laureate Archibald Vivian Hill.
The studies that would become perhaps the most influential in the history of the exercise sciences were performed by Hill and his colleagues at University College, London between 1923 and 1925 (Hill and Lupton, 1923
; Hill et al., 1924a
). But Hill’s personal beliefs of what causes fatigue predetermined his interpretation of the results of his quite simple experiments. Thus his conclusions and, as a result, the intellectual direction down which his ideas channeled the exercise sciences were determined by Hill’s preconceptions even before he undertook his first experiment (Noakes, 1997
). His personal beliefs were fashioned by at least three factors.
Firstly since he was principally a muscle physiologist, it was naturally that Hill’s theories would begin from that perspective.
Secondly were a series of studies performed at Cambridge University by another Nobel Laureate Frederick Gowland Hopkins. The crucial 1907 study (Fletcher and Hopkins, 1907
) that influenced Hill’s thinking had been designed to develop a novel method accurately to measure muscle lactate concentrations in recently killed laboratory animals, specifically frogs. By plunging excised frog muscles into ice-cold alcohol, Fletcher and Hopkins were able to show that lactate concentrations were elevated in muscles that had been stimulated to contract until failure. We now know that ice-cold alcohol denatures the glycolytic enzymes activated by ischemia and anoxia and the activation of which cause muscle lactate concentrations to increase in ischemia and hypoxia. Fletcher and Hopkins also showed that skeletal muscle lactate concentrations fell in muscles stored in a high oxygen concentration and conversely rose when stored in nitrogen.
As a result Fletcher and Hopkins concluded that: “Lactic acid is spontaneously developed, under anaerobic conditions, in excised muscle” so that “the accumulation of lactic acid in muscle occurs only in the conditions of anaerobiosis. With a proper oxygen supply it fails to accumulate at all.” They also wrote that: “Fatigue due to contractions is accompanied by an increase of lactic acid.”
But Hill’s interpretation of these results was more doctrinaire specifically (a) that lactic acid is produced only under conditions of muscle anaerobiosis, and (b) that muscle fatigue is caused by increased muscle lactate concentrations. These ideas would form the twin pillars of Hill’s nascent theory of the factors that cause fatigue and determine human athletic performance.
Thirdly were studies published in 1909 and 1910 (Hill and Mackenzie, 1909
; Hill and Flack, 1910
) apparently showing that the inhalation of oxygen significantly improved performance during exercise. This led to the conclusion that “this limit (to muscular work) is imposed by the supply of oxygen to the muscles and brain rather than by the function of the skeletal muscles” (Bainbridge, 1919
, p. 133) so that “the supply of oxygen to the body is the decisive factor in setting the limit to exercise” (Bainbridge, 1919
, p. 136).
As a result of studies conducted on himself when he ran at 10, 12, and 16
km/h around an 84.5
m track near the Physiological Laboratory, Manchester, Hill concluded that increasing muscle lactate (lactic acid) concentrations secondary to the development of skeletal muscle anaerobiosis, caused the fatigue he experienced when running at 16
km/h. Accordingly he developed a model of human exercise physiology (Figure ) that has dominated teaching and research in the exercise sciences ever since (Mitchell et al., 1958
; Mitchell and Blomqvist, 1971
; Bassett Jr. and Howley, 1997
; Mitchell and Saltin, 2003
; Levine, 2008
The complete A. V. Hill Cardiovascular/Anaerobic/Catastrophic Model of Human Exercise Performance. The governor component causing a “slowing of the circulation” was lost from the model some time after the 1930s.
Hill’s model predicts that shortly before the termination of maximal exercise the oxygen demands of the exercising muscles exceed the (limiting) capacity of the heart to supply that oxygen. This causes skeletal muscle anaerobiosis with the accumulation of “poisonous” lactate (lactic acid) in the muscles. So Hill believed that the heart’s capacity to pump a large volume of blood to the active skeletal muscles was the single factor determining the human’s ability to perform maximal exercise since the higher the blood supply to muscle, the greater the exercise intensity that could be achieved before the onset of anaerobiosis and fatigue.
Remarkably the most interesting component of Hill’s model is that which has been (conveniently) ignored for the past 90
years. For his model invites the really important question: if the heart’s capacity to produce a maximum cardiac output indeed limits maximum exercise performance, then what limits the maximal cardiac output? This is the key question that has been systematically ignored by all who have favored Hill’s theory for the past 90
Hill believed that the answer was obvious – specifically the development of myocardial ischemia the instant the maximum (limiting) cardiac output was reached. Indeed this would be the modern conclusion since it is established that the development of myocardial ischemia during exercise impairs cardiac function, producing a progressive left ventricular dilatation as a result of impaired myocardial contractility (Rerych et al., 1978
So Hill’s complete model theorized that maximal exercise is limited by the development of myocardial failure consequent to the development of myocardial ischemia. This model is “catastrophic” since it predicts that exercise is limited by a failure of homeostasis, in this case in the regulation of cardiac function.
This model soon became the standard teaching in the textbooks of the day (Bainbridge, 1931
): “The blood supply to the heart, in many men, may be the weak link in the chain of circulatory adjustments during muscular exercise, and as the intensity of muscular exertion increases, a point is probably reached in most individuals at which the supply of oxygen to the heart falls short of its demands, and the continued performance of heavy work becomes difficult or impossible” (pp. 175–176).
Mosso’s concept that the nervous system could also be the site of fatigue was not entirely abandoned. For the 1931 edition (Bainbridge, 1931
) of Bainbridge’s original monograph (Bainbridge, 1919
), edited at A. V. Hill’s request by the American physiologists A. V. Bock and D. B. Dill, includes the following statement: “There appear, however, to be two types of fatigue, one arising entirely within the central nervous system, the other in which fatigue of the muscles themselves is superadded to that of the nervous system” (p. 228). But this concept of central fatigue, perhaps borrowed from Mosso, would soon disappear from the teaching of the exercise sciences as the idea became entrenched that peripheral fatigue, situated exclusively in the skeletal muscles, explains all forms of exercise fatigue.
But Hill had not completed his model; he added one final and decisive embellishment to his model. He concluded that some mechanism must exist to protect the ischemic heart from damage whilst it continues to contract until the “poisoning” of the skeletal muscles causes the exercise finally to terminate. So he proposed that a “governor” either in the heart or brain reduces the pumping capacity of the heart immediately this inevitable myocardial ischemia develops. By causing a “slowing of the circulation” (Hill et al., 1924a
) this governor would protect the ischemic myocardium from damage in this critical period before the exercise terminated.
But sometime after World War II, Hill’s concept of a “governor” mysteriously disappeared from the next generation of exercise physiology textbooks, perhaps because the introduction of electrographically monitored maximal exercise testing established that the healthy heart does not become ischemic even during maximal exercise (Raskoff et al., 1976
). Instead the presence of electrocardiographic evidence of ischemia soon became an important diagnostic tool for the detection of coronary artery disease; the absence of these signs of ischemia was interpreted as evidence that the heart is healthy (Lester et al., 1967
But instead of concluding that the absence of myocardial ischemia during maximal exercise disproves the Hill model, succeeding generations of exercise physiologists simply removed this inconvenient component from their adopted model. Instead they have continued to preach, as fact, the original Hill hypothesis that a limiting cardiac output is the sole important regulator of human exercise performance.
Indeed the special 2008 Olympic Games edition of the influential Journal of Physiology
includes the statement that: “(2) the primary distinguishing characteristic of elite endurance athletes that allows them to run 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” (Levine, 2008
, p. 31).
Like the Hill model, this explanation continues to interpret fatigue as a “catastrophic” event that occurs only after skeletal muscle function has failed, specifically “severe functional alterations at the local muscle level.” Overlooked is Mosso’s conclusion that fatigue is “one of its (the human body’s) most marvelous perfections.”
But Levine does acknowledge that his description cannot adequately explain why athletes ultimately choose to stop exercising. So he adds that which Hill did not: “(3) athletes stop exercising at
because of severe functional alterations 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” (p. 31). This explanation differs from the original Hill model that hypothesizes that some form of central motor command slows the functioning of the heart not the skeletal muscles. It is however entirely compatible with the action of a central governor (Noakes, 2011b
). Paradoxically one aim of Levine’s article was to discredit the concept of such a governor.