WASSERMAN, KARLMAN, BRIAN J. WHIPP, SANKAR IX KOYAL, AND WILLIAM L. BEAVER. Anaerobic threshold and respiratory gas exchange during exercise. J. Appl. Physiol. 35(Z): 236-243. 1973.-Alterations in gas exchange were studied in man during exercise increasing in increments of 15 w each minute, to determine the noninvasive indicators of the onset of metabolic acidosis (anaerobic metabolism). Expired airflow and CO 2 and 0 2 tensions at the mouth during the breath were continuously monitored with rapid1 y responding gas analyzers. These measurements were recorded directly as well as processed by a minicomputer, on-line, to give minute ventilation (VE), COP production #co& 02 consumption (voz), and the gas exchange ratio (R), breath-by-breath. The anaerobic threshold (AT) could be identified by the point of I) nonlinear increase in VE, 2) nonlinear increase in Vco2, 3) an increase in end-tidal 02 without a corresponding decrease in endtidal COz, and 4) an increase in R, as work rate was increased during an incremental exercise test. Of these measurements, R was found least sensitive. The AT was determined in 85 normal subjects between 17 and 91 years of age, by these techniques. The lower limit of normal was 45 w (KTo 2 = 1 liter/min), while values for very fit normal adults were as high as 180 w. The patients studied with cardiac disease above functional class I have lower anaerobic thresholds than the least fit normal subjects. The I-min incremental work rate test is associated with changes in gas exchange which can be used as sensitive on-line indicators of the AT, thus bypassing the need for measuring arterial lactate or acid-base parameters to indicate anaerobiosis.

Anaerobic threshold and respiratory gas exchange during exercise.

For much of the 20th century, lactate was largely considered a dead-end waste product of glycolysis due to hypoxia, the primary cause of the O2 debt following exercise, a major cause of muscle fatigue, and a key factor in acidosis-induced tissue damage. Since the 1970s, a ‘lactate revolution’ has occurred. At present, we are in the midst of a lactate shuttle era; the lactate paradigm has shifted. It now appears that increased lactate production and concentration as a result of anoxia or dysoxia are often the exception rather than the rule. Lactic acidosis is being re-evaluated as a factor in muscle fatigue. Lactate is an important intermediate in the process of wound repair and regeneration. The origin of elevated [lactate] in injury and sepsis is being re-investigated. There is essentially unanimous experimental support for a cell-to-cell lactate shuttle, along with mounting evidence for astrocyte–neuron, lactate–alanine, peroxisomal and spermatogenic lactate shuttles. The bulk of the evidence suggests that lactate is an important intermediary in numerous metabolic processes, a particularly mobile fuel for aerobic metabolism, and perhaps a mediator of redox state among various compartments both within and between cells. Lactate can no longer be considered the usual suspect for metabolic ‘crimes’, but is instead a central player in cellular, regional and whole body metabolism. Overall, the cell-to-cell lactate shuttle has expanded far beyond its initial conception as an explanation for lactate metabolism during muscle contractions and exercise to now subsume all of the other shuttles as a grand description of the role(s) of lactate in numerous metabolic processes and pathways.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2003.058701

Lactate metabolism: a new paradigm for the third millennium

The development of acidosis during intense exercise has traditionally been explained by the increased production of lactic acid, causing the release of a proton and the formation of the acid salt s...

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Biochemistry of exercise-induced metabolic acidosis

The measurement of the respiratory gas exchange ratio (R) during a standard exercise test is used to detect the onset of anaerobic metabolism during exercise, which results from failure of the cardiovascular system to supply the oxygen requirements of the tissues. The method described uses end-tidal gas concentrations to calculate R while the exercise test is taking place. Blood sampling is unnecessary, and the results can be determined during the test, thus avoiding exhaustive exercise. The method provides an objective measurement of one of the factors influencing exercise tolerance.

Detecting the threshold of anaerobic metabolism in cardiac patients during exercise

Arterial concentrations and substrate exchange across the leg and splanchnic vascular beds were determined for glucose, lactate, pyruvate, glycerol, individual acidic and neutral amino acids, and free fatty acids (FFA) in six subjects at rest and during 4 h of exercise at approximately 30% of maximal oxygen uptake. FFA turnover and regional exchange were evaluated using (14)C-labeled oleic acid. The arterial glucose concentration was constant for the first 40 min of exercise, but fell progressively thereafter to levels 30% below basal. The arterial insulin level decreased continuously, while the arterial glucagon concentration had risen fivefold after 4 h of exercise. Uptake of glucose and FFA by the legs was markedly augmented during exercise, the increase in FFA uptake being a consequence of augmented arterial levels rather than increased fractional extraction. As exercise was continued beyond 40 min, the relative contribution of FFA to total oxygen metabolism rose progressively to 62%. In contrast, the contribution from glucose fell from 40% to 30% between 90 and 240 min. Leg output of alanine increased as exercise progressed. Splanchnic glucose production, which rose 100% above basal levels and remained so throughout exercise, exceeded glucose uptake by the legs for the first 40 min but thereafter failed to keep pace with peripheral glucose utilization. Total estimated splanchnic glucose output was 75 g in 4 h, sufficient to deplete approximately 75% of liver glycogen stores. Splanchnic uptake of gluconeogenic precursors (lactate, pyruvate, glycerol, alanine) had increased 2- to 10-fold after 4 h of exercise, and was sufficient to account for 45% of glucose release at 4 h as compared to 20-25% at rest and at 40 min of exercise. In the case of alanine and lactate, the increase in precursor uptake was a consequence of a rise in splanchnic fractional extraction. It is concluded that during prolonged exercise at a low work intensity (a) blood glucose levels fall because hepatic glucose output fails to keep up with augmented glucose utilization by the exercising legs; (b) a large portion of hepatic glycogen stores is mobilized and an increasing fraction of the splanchnic glucose output is derived from gluconeogenesis; (c) blood-borne substrates in the form of glucose and FFA account for a major part of leg muscle metabolism, the relative contribution from FFA increasing progressively; and (d) augmented secretion of glucagon may play an important role in the metabolic adaptation to prolonged exercise by its stimulatory influence on hepatic glycogenolysis and gluconeogenesis.

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Substrate Turnover during Prolonged Exercise in Man: SPLANCHNIC AND LEG METABOLISM OF GLUCOSE, FREE FATTY ACIDS, AND AMINO ACIDS

Although direct evidence of a quantitative relationship between oxygen debt and lactic acid production in man has never been given, there is general agreement with A. V. Hill’s hypothesis that the oxygen debt is due to the delayed oxidation of a fraction of the lactic acid produced during the anaerobi .c processes of muscular activity. After the “revolution” produced in muscle physiology by the discoveries of the last few years, m ainiy after Lundsgaard’s work, and the further observations on men, it seemed to us that the lactic acid mechanism alone is inadequate to explain all the processes which occur in the payment of the oxygen debt, particularly for the following reasons: a. It has been observed in isolated muscle that most of the lactic acid is produced after the contraction is over, during the first minute of recovery; this does not seem to agree with the fact that the payment of the oxygen debt at the beginning shows no lag even if the exercise is of very short duration. b. In moderate exercise of long duration in man, involving an oxygen debt of 3 to 4 liters, the changes in lactic acid concentration or in pH of blood are negligible in comparison with the values implied by the assumption of an increment of lactic acid in the body corresponding to the amount of oxygen debt. (See, for the lactic acid concentration in blood following muscular exercise, Owles, 1930; Dill, Edwards, Foiling, Oberg, Pappenheimer and Talbott, 1931; for data on pH, Margaria and Talenti, 1933.) c. There exist oxidative recovery processes following muscular contraction other than the glycogen resynthesis from lactic acid ; Lundsgaard (1931) has demonstrated in muscles poisoned with iodoacetic acid the partial resynthesis of the phosphocreatine in the presence of oxygen and in the absence of any lactic acid formation or remo val; Clark, Eggleton and

The possible mechanisms of contracting and paying the oxygen debt and the rôle of lactic acid in muscular contraction

Biomechanics and Energetics of Muscular Exercise

The many observations on blood sugar in exercise have revealed widely different conditions. Thus one may have extreme hypoglycemia as found by Levine, Burgess and Derick (1) in some marathon runners, or at the other extreme, hyperglycemia as in football players (2). A moderate decrease in the concentration of sugar in the blood (B. S.) has been found by Christiansen (3) in exercise of one hour’s duration; in recovery following exercise both Rakestraw (4) and Christiansen report moderate increases. We have found that when exercise is carried on for many hours without emotional stress the value of B. S. may not vary much from the resting level until a terminal hypoglycemia develops (5). It seems probable that such a state reflects the exhaustion of glycogen reserves; if so it should be associated with a decreasing respiratory quotient. With this possibility in mind we have undertaken a series of experiments designed to study the relation between metabolic rate (M. R.), respiratory quotient (R. Q.), carbohydrate reserve,l and blood sugar (B. S.). The experimental procedure has been described in part elsewhere (6). In these experiments two rates of work were employed with alternation of rate each half-hour. The work was carried on for several hours, tiz., long enough to reduce materially the reserve of carbohydrate. During each half-hour blood was obtained from the finger while work proceeded and sugar was determined by the Folin-Malmros method (7). At the same time expired air was collected and analyzed in the usual manner. Since the rate of work did not exceed the oxygen transport capacity the rate of oxygen intake is a measure of the M. R. Our ablest subject was Y, aged 19, a skilled runner who has finished near the front in marathons. In three experiments he ran for 6 hours alternating at rates of 9.3 and 11.3 km. per hour with an energy output on these occasions averaging 3400 Cals. The second of’these experiments

Metabolic rate, blood sugar and the utilization of carbohydrate.

Es wurden Bestimmungen der Arbeitsfahigkeit des Menschen bei verschiedenem Luftdruck ausgefuhrt.

Die Arbeitsfähigkeit des Menschen bei vermindertem Luftdruck

Recovery processes have been studied in severe work of uniform intensity continuing from a minimum of 5 seconds to a maximum of 106 seconds The work was largely anaerobic, requiring the accumulation of an oxygen debt, the magnitude of which was approximately a linear function of time

R. Margaria

Papers

The possible mechanisms of contracting and paying the oxygen debt and the rôle of lactic acid in muscular contraction

Biomechanics and Energetics of Muscular Exercise

Metabolic rate, blood sugar and the utilization of carbohydrate.

Die Arbeitsfähigkeit des Menschen bei vermindertem Luftdruck

Analysis of recovery from anaerobic work