Comments on classical papers.

WHAT IS THE ROLE OF LACTIC ACID in muscle contraction and at the whole body level? Since the beginning of the 20th century physiologists have known that when an isolated, unperfused frog muscle was stimulated to contract, lactic acid was produced as part of the contractile response and that oxygen was necessary during recovery to metabolize the lactic acid to eliminate its presence. These phenomena formed the HillMeyerhof “O2 debt” theory, which proposed that during recovery, one-fifth of the lactate was oxidized to provide energy for converting four-fifths of the produced lactate back to glycogen (7–9). The findings, in part, resulted in the Nobel Prize being awarded to A. V. Hill and Otto Meyerhof in 1922. Subsequently, in 1933, Margaria, Edwards, and Dill at the Harvard Fatigue Laboratory, published their seminal paper, which attempted to elaborate on the oxygen debt theory by studying the oxygen consumption and blood lactate kinetics in human subjects during and after short-duration treadmill exercise of high intensities (4–10 min). Their key findings were that 1) recovery oxygen consumption rapidly declined initially and then slowly tailed off toward resting values, a process that took approximately 1 h, and 2) the high level of lactic acid that was present in the blood at the end of exercise did not decline immediately and then it declined slowly with kinetics, approximating the observed pattern of the oxygen consumption response. Therefore, Margaria and associates surmised that the first fast phase of the postexercise oxygen consumption curve was not temporally associated with a change in blood lactate. This phase was termed “alactacid,” meaning not associated with lactate metabolism. Also, they proposed that the second, slow postexercise O2 consumption curve, which temporally coincided with the decline in blood lactate, was due to the reconversion of lactate to glycogen. Thus this slow phase was termed the “lactacid” component of the oxygen debt. This paper was significant, not only for defining two phases of the oxygen debt response, but also for conceptually departing from the classical work of Meyerhof and Hill and coworkers. As history would prove, they were largely correct concerning the alactacid component, inasmuch as collective observations suggest that the alactacid component is largely attributed to the oxidative replenishment of high-energy phosphagen stores that are rapidly broken down during the initial phases of the exercise response before oxygen consumption reaches a true metabolic steady state for covering the energy requirements. The subsequent replenishment of these compounds, which occurs very rapidly in the muscles after exercise, is indeed not linked to lactate metabolism. However, with regard to the lactacid component of the O2 debt, Margaria and associates were clearly incorrect concerning the contribution of lactate metabolism in accounting for the extra oxygen (e.g., the lactacid oxygen debt) consumed during recovery. On the basis of their experimental design of using only short-duration exercise before the recovery protocols, these investigators could not have known that, in fact, lactate was rapidly entering and leaving the blood immediately after exercise and that oxidation was the major fate of lactate during both exercise and recovery. Nevertheless, the world came to know and accept the hypothesis of the lactic and alactacid oxygen debts. However, it took several decades to unravel further insightful research on this topic as spearheaded by the work of Margaria, Edwards, and Dill. A brief synopsis of the highlights of this subsequent work is summarized below.