Respiration Physiology 118 (1999) 103–115The energetics of anaerobic muscle metabolism: areappraisal of older and recent conceptsPietro Enrico di Pramperoa, Guido Ferrettib,*aDipartimento di Scienze e Tecnologie Biomediche, Uni6ersita` di Udine, Piazzale Kolbe4, I-33100Udine, ItalybDe´partement de Physiologie, Centre Me´dical Uni6ersitaire,1rue Michel Ser6et, CH-1211Gene`6e4, SwitzerlandAccepted 24 August 1999AbstractThis paper discusses under an energetic perspective the recent and older evidence supporting the classical notionthat the ‘oxygen debt’, as originally defined by Margaria et al. (1933) [Am. J. Physiol. 106, 689 –714], consists of twomajor components: the alactic oxygen debt, with a half-time of the order of 30 sec, and the lactic oxygen debt, witha much longer half-time, similar to that of lactic acid removal from blood after exercise (: 15 min). In particular, twoensuing concepts are treated, namely (i) the energetic equivalent of blood lactate accumulation in blood, whence thenotions of lactic power and lactic capacity, and (ii) the energy sources allowing contraction of the oxygen deficit atthe onset of square-wave exercise. The notion of alactic oxygen deficit is rediscussed on the basis of recent evidencein humans. The analogies between lactate accumulation during supramaximal exercise and during exercise transientsare discussed under an energetic perspective. © 1999 Elsevier Science B.V. All rights reserved.Keywords:Exercise, energetics; Lactic acid, removal; Lactic acid, energy equivalent; Mammals, humans; Muscle, skeletal, lactic acid;Oxygen, debtwww.elsevier.com/locate/resphysiol1. IntroductionThe aim of this paper is to review briefly about40 years of a main chapter of the history of theenergetics of muscular exercise, namely that of theanaerobic energy sources. It seems fair to sayfrom the outset that we will not try to present acomprehensive review of the matters at stake. Wewill rather focus on facts and theories generatedby the ‘School of Margaria’ from the early sixtiesonwards, not only because this paper is dedicatedto Paolo Cerretelli, who was and still is one of theleaders among Rodolfo Margaria’s heirs, but alsoand especially because we are convinced that theconcepts created by the School of Margaria, andsummarized below, can provide a solid back-ground and a good starting point for many as yetunanswered questions.Dedicated to Professor Paolo Cerretelli on the occasion ofhis retirement from a chair of physiology at the University ofGeneva, Switzerland.* Corresponding author. Tel.: +41-22-702-5363; fax: +41-22-702-5402.E-mail address:[email protected] (G. Fer-retti)0034-5687/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved.PII: S0034-5687(99)00083-3P.E. di Prampero, G. Ferretti/Respiration Physiology118 (1999) 103 – 115104In 1933, a paper entitled ‘The possible mecha-nism of contracting and paying the oxygen debtand the role of lactic acid in muscular contrac-tion’, was published in the American Journal ofPhysiology (Margaria et al., 1933). This paper,indeed a seminal one, introduced the concept of‘alactic oxygen debt’, and for this very reasoninitiated a revolution in the physiology of muscu-lar exercise. The ‘phosphagens’ had been recentlyidentified (Eggleton and Eggleton, 1927; Fiskeand Subbarow, 1927; Lohmann, 1928), and anumber of ensuing observations on isolated mus-cle contraction was casting a shadow over Hilland Meyerhof’s theory of the energetics of musclecontraction (Hill, 1932; for a review see Needham,1971). According to this theory, for which Hilland Meyerhof were awarded the Nobel Prize forMedicine or Physiology in 1923, oxidation ofglycogen to lactic acid is the main energy sourcefor muscular contraction, whereas oxygen is con-sumed for oxidising a fraction of the accumulatedlactic acid, so yielding the energy for the resynthe-sis to glycogen of the remaining fraction (Hill,1924). Margaria et al. (1933), by means of amathematical analysis of the oxygen consumptioncurve after heavy exercise in man, demonstratedthat a substantial fraction of the oxygen debtpayment is independent of lactic acid removalfrom blood. As a consequence, they subdividedthe overall oxygen debt in two major components:the alactic oxygen debt, with a shorter time con-stant t (half-time, t1/2=t ln 2: 30 sec), and thelactic oxygen debt, with a much longer t1/2, similarto that of lactic acid removal from blood afterexercise ( : 15 min).These findings generated a brilliant refutationof Hill and Meyerhof’s theory, representing amajor step forward on the way to our presentunderstanding of the energetics of muscle contrac-tion. Margaria et al. (1933) had studied the kinet-ics of the oxygen debt payment. The time hadcome of challenging Margaria’s concept of oxygendebt by studying the way it was incurred at theonset of exercise. Apart from the isolated pioneer-ing work of Henry (1951) on exercise transients,this task was essentially undertaken in the earlysixties by a group of scientists in Milano, amongwhom Cerretelli played a major role, under theintellectual leadership of Rodolfo Margaria.This led to the creation of two basic concepts inthe energetics of muscular exercise: (i) the en-ergetic equivalent of blood lactate accumulationin blood, whence the notions of lactic power andlactic capacity, and (ii) the obligatory fraction ofoxygen deficit at the onset of exercise. Theseconcepts are discussed, under a historical perspec-tive, in the present paper. The paper is thereforedivided in two sections, the first devoted to ananalysis of the anaerobic lactic energy sources, thesecond to the energetics of the oxygen deficit anddebt.2. The anaerobic energy sources2.1. The energy equi6alent of lactic acidformationMargaria et al. (1963a) determined the energycost of running at various speeds and inclines ofthe terrain, allowing an estimate of the corre-sponding metabolic power requirements. So theMilano group set out to determine the rate oflactate accumulation in blood at speeds and in-clines requiring a metabolic power larger thanthat corresponding to the subjects’ maximal oxy-gen consumption (Margaria et al., 1963b). Eachconstant supramaximal speed trial was subdividedinto several bouts of increasing duration, untilvolitional exhaustion. After each bout, the subjectwas asked to rest and the lactic acid concentrationin blood measured throughout the recovery pe-riod. Assuming that (i) the