Mechanical and metabolic determination of VO2 and fatigue during repetitive isometric contractions in situ.

Repetitive isometric tetanic contractions (1/s) of the canine gastrocnemius-plantaris muscle were studied either at optimal length (Lo) or short length (Ls; approximately 0.9 . Lo), to determine the effects of initial length on mechanical and metabolic performance in situ. Respective averages of mechanical and metabolic variables were (Lo vs. Ls, all P < 0.05) passive tension (preload) = 55 vs. 6 g/g, maximal active tetanic tension (Po) = 544 vs. 174 (0.38 . Po) g/g, maximal blood flow (Q) = 2.0 vs. 1.4 ml . min-1 . g-1, and maximal oxygen uptake (VO2) = 12 vs. 9 micromol . min-1 . g-1. Tension at Lo decreased to 0.64 . Po over 20 min of repetitive contractions, demonstrating fatigue; there were no significant changes in tension at Ls. In separate muscles contracting at Lo, Q was set to that measured at Ls (1.1 ml . min-1 . g-1), resulting in decreased VO2 (7 micromol . min-1 . g-1), and rapid fatigue, to 0.44 . Po. These data demonstrate that 1) muscles at Lo have higher Q and VO2 values than those at Ls; 2) fatigue occurs at Lo with high VO2, adjusting metabolic demand (tension output) to match supply; and 3) the lack of fatigue at Ls with lower tension, Q, and VO2 suggests adequate matching of metabolic demand, set low by short muscle length, with supply optimized by low preload. These differences in tension and VO2 between Lo and Ls groups indicate that muscles contracting isometrically at initial lengths shorter than Lo are working under submaximal conditions.

Blood flow and pressure relationships which determine VO2max.

The role of O2 delivery in regulating VO2max has been studied in an isolated gastrocnemius-plantaris muscle preparation contracting in situ; recent data addressing this issue are presented. VO2 increases nonlinearly with stimulation frequency reaching a peak at 5 twitches.s-1 or 1 tet.s-1 (200 ms trains, 50 imp.s-1). Further increases in stimulation frequency result in a lower VO2. Measured VO2 maxima are less than predicted VO2 capacity, and peak VO2 during tetanic contractions is greater than that during twitches. Above 150 imp.min-1, VO2 is directly related to the level of blood flow attained as VO2/Q (arterial-venous O2 difference) is fixed by some unknown mechanism. Increasing blood flow, with a pump, during 1.s-1 tetanic contractions increases O2 diffusive conductance and peak VO2. When O2 delivery is reduced, ischemic hypoxia appears to result in more rapid reductions in muscle performance than hypoxic hypoxia because of decreases in perfusion pressure and Q. 31P-NMR studies reveal that reductions in creatine phosphate and energy charge are similar between ischemia and hypoxia suggesting a common regulator, O2. We conclude that VO2max is limited by O2 delivery as a result of a limited and uneven distribution of muscle blood flow. These limitations appear secondary to mechanical restraints imposed by contraction duty cycle and vascular compression.

Muscle blood flow and distribution determine maximal VO2 of contracting muscle.

During repetitive contractions, the VO2 of the dog gastrocnemius-plantaris muscle rose with the contraction frequency up to a maximal value and then decreased as contraction frequency was increased further. PVO2 was constant over most of the contraction frequency range. Reducing perfusion pressure/blood flow reduced VO2max with a constant PVO2. During these maneuvers the diffusion conductance, DCO2 (VO2/PVO2), changed with VO2. Raising the perfusion pressure/flow with a pump increased VO2 with a small rise in PVO2 so that DCO2 also increased. Removing tension from the muscle between contractions elevated VO2 and DCO2 without a change in perfusion pressure. Hypoxemia decreased VO2 with a decrease in PVO2; DCO2 remained constant. A three-compartment mathematical model, based on microsphere measurements of regional flow, was used to illustrate how regional flow variations may exist, and how they are poorly revealed in the mixed whole-muscle venous blood. The model shows VO2.g-1 strongly related to flow. As VO2.g-1 increased as Q.g-1 increased, extraction decreased, and DCO2 increased.

Preload release increases blood flow and decreases fatigue during repetitive isotonic muscle contractions.

The effects of preload on blood flow (Q), O2 uptake (VO2), and fatigue were investigated in the canine gastrocnemius-plantaris muscle in situ. Repetitive (1 contraction/s, 200 ms duration) afterloaded (0.25-0.3 maximal active isometric tension) isotonic tetanic contractions were performed in high-preload (HP; 69 g/g, n = 5), low-preload (LP; 35 g/g, n = 6), and preload-release (PR; 0 g/g, n = 5) experiments. Maximal Q values (1.0, 1.6, and 2.1 ml.min-1.g-1, P < 0.05 for all comparisons) and Q2 delivery (8, 13, and 17 mumol.min-1.g-1, P < 0.05 for all comparisons) increased significantly with decreasing preload. The maximal VO2 of HP was 7.2 mumol.min-1.g-1, which is significantly lower than both LP (10.5 mumol.min-1.g-1, P < 0.05) and PR values (11.4 mumol.min-1.g-1, P < 0.05); these differences were sustained through 20 min of contractions. Fatigue, measured as a loss of power production, was 63, 37, and 23% at 20 min of contractions in HP, LP, and PR, respectively, indicating significantly less fatigue with decreasing preload (P < 0.05 for all comparisons). These data demonstrate that the preload, present as the level of passive tension maintained between contractions, can influence Q, VO2, and fatigue during repetitive isotonic tetanic contractions of muscle in situ by a mechanically determined metabolic modulation of dynamic muscle performance.

Metabolic and work capacity of skeletal muscle of PFK-deficient dogs studied in situ.

Mechanical and metabolic relationships of muscle lacking phosphofructokinase (PFKD) activity were compared with muscle having normal phosphofructokinase (NORM) activity by using the gastrocnemius-plantaris muscle group with isolated circulation in situ. Muscle contractile properties were similar in both groups. Initial power output (W) during repetitive tetanic (200 ms, 50 impulses/s) isotonic contractions was similar in both groups; however, W declined significantly more (30-80%) in PFKD than in NORM muscle over time, with a constant O2 uptake (VO2)/W. Despite similar O2 and substrate delivery, PFKD muscle had a lower VO2 (42-55%), less glucose uptake, similar free fatty acid uptake, and lactic acid uptake rather than output, during contractions. Muscle venous H+ concentration, strong ion difference, and PCO2 increased during contractions, the magnitude of change being smaller in PFKD muscle. Elevating arterial lactate concentration before contractions in PFKD muscle resulted in significant improvements in W and VO2 without altering the acid-base exchange at the muscle. Increasing O2 delivery by increasing arterial O2 concentration in PFKD dogs did not improve W or VO2. We conclude that, despite no inherent mechanical or contractile differences, PFKD muscle has a severely limited oxidative capacity and exaggerated fatigue and blood flow responses to contractions due to limited substrate metabolism resulting from the inability to utilize glycogen and/or glucose.

Lactate and acid-base exchange during brief intense contractions of skeletal muscle in situ.

Our goal was to design a stimulation-contraction paradigm using an isolated in situ dog gastrocnemius muscle preparation that would provide an experimental model for brief intense intermittent (IC) exercise in humans. Second, acid-base and ion exchanges across the muscle were investigated using four 30-s bouts of isotonic tetanic contractions (2 s-1, 100-ms train, 50 impulses/s) with 4 min of rest between bouts. During the bouts, peak power output (W) was 18.2 mW/g in the first bout; it declined by 4.4% by the fourth bout and by 12-16% in each bout. Compared with repetitive continuous contractions (CC) at maximal O2 uptake (VO2), W was greater and VO2 (approximately 3.5 mumol.g-1.min-1) and CO2 production (approximately 4.5 mumol.g-1.min-1) were less with IC. Venous-arterial (v-a) differences and lactate output peaked immediately after each bout and were not different from the values reported for CC at maximal VO2. Thus, with IC, VO2/W was lower and the CO2 production/VO2 and lactate output/VO2 ratios were greater than those seen with CC. These differences suggest that this stimulation-contraction paradigm may be an appropriate model for brief intense exercise. The v-a [H+] difference was a direct result of the v-a PCO2 difference. The venous strong ion difference was always greater than or equal to the arterial strong ion difference because the v-a [Cl-] difference was opposite and greater than the v-a lactate concentration difference, whereas the v-a [Na+] and [K+] differences were small.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow elevation increases VO2 maximum during repetitive tetanic contractions of dog muscle in situ.

Blood flow through the gastrocnemius-plantaris muscle of the dog in situ was increased by a pump in the arterial supply during a 30-min period of 1/s isotonic tetanic contractions. Compared with a control series of experiments with normoxemia and spontaneous flow, the pump increased flow 84%, from 1.51 +/- 0.08 to 2.78 +/- 0.15 ml.g-1.min-1. The perfusion pressure was increased from 125 to 196 mmHg. The pump hyperemia increased maximal O2 uptake (VO2) at 5 min of contractions by 31%, from 8.97 +/- 0.44 to 12.89 +/- 0.30 mumol.g-1.min-1. The extraction was decreased, and venous PO2 (PVO2) was increased. Fatigue, measured as a drop in power production from the highest level at 10 s to 30 min, was 49% during pump hyperemia and 54% in the control conditions. VO2 decreased 30% from the 5-min value to the 30-min value with pump hyperemia and 28% over the same time in the control conditions. At maximal VO2, the ratio VO2/PVO2 was increased by pump hyperemia compared with control conditions, suggesting an increased O2 diffusing conductance of the muscles. We conclude that the elevated perfusion pressure of pump hyperemia increased flow to raise maximal VO2 mainly in areas of the muscle that had restricted flow under control conditions.

Force-velocity shifts with repetitive isometric and isotonic contractions of canine gastrocnemius in situ.

The force-velocity (F-V) relationships of canine gastrocnemius-plantaris muscles at optimal muscle length in situ were studied before and after 10 min of repetitive isometric or isotonic tetanic contractions induced by electrical stimulation of the sciatic nerve (200-ms trains, 50 impulses/s, 1 contraction/s). F-V relationships and maximal velocity of shortening (Vmax) were determined by curve fitting with the Hill equation. Mean Vmax before fatigue was 3.8 +/- 0.2 (SE) average fiber lengths/s; mean maximal isometric tension (Po) was 508 +/- 15 g/g. With a significant decrease of force development during isometric contractions (-27 +/- 4%, P < 0.01, n = 5), Vmax was unchanged. However, with repetitive isotonic contractions at a low load (P/Po = 0.25, n = 5), a significant decrease in Vmax was observed (-21 +/- 2%, P < 0.01), whereas Po was unchanged. Isotonic contractions at an intermediate load (P/Po = 0.5, n = 4) resulted in significant decreases in both Vmax (-26 +/- 6%, P < 0.05) and Po (-12 +/- 2%, P < 0.01). These results show that repeated contractions of canine skeletal muscle produce specific changes in the F-V relationship that are dependent on the type of contractions being performed and indicate that decreases in other contractile properties, such as velocity development and shortening, can occur independently of changes in isometric tension.

Regulation of muscle lactate production.

It is not possible to make accurate measurements of muscle lactic acid net exchange during exercise by application of the Fick relationship. To make accurate measurements of lactic acid net exchange, preparations with isolated circulations have been used. Since such preparations utilize relatively small muscles or groups of muscles, the data apply to muscle contractions, not exercise. In exercise, external influences may affect lactate exchange. The net lactic acid exchange (L) of the isolated dog gastrocnemius-plantaris muscle group has been quantified for repetitive twitch and tetanic contractions, progressive contractions, and four repetitions of 30-s intense contractions with 3.5 min of recovery between each. Epinephrine has been infused during repetitive and progressive contractions; modest ischemia and hypoxic hypoxia, and the oxidation-reduction state of mitochondrial cytochrome a-a3 have been investigated. After the initiation of repetitive contractions, L rises transiently to a peak at 3-5 min and then declines to net uptake after 30 min of contractions. The peak L is roughly proportional to VO2. L rises progressively during progressive contractions to levels lower than the peak in repetitive contractions. Epinephrine increases L transiently during repetitive contractions and increases L during progressive contractions. L rises to levels similar to the repetitive peak during the four repeated 30-s bouts. Cytochrome a-a3 was more oxidized during contractions than when at rest. Ischemia has little or no effect on L. Hypoxic hypoxia sufficient to produce hypoxidosis increased L sharply, but transiently. Muscle L reflects the balance between the production of the products of glycolysis and their removal into the mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences between VO2 maxima of twitch and tetanic contractions are related to blood flow.

The purpose of this investigation was to compare oxygen uptake (VO2) and fatigue characteristics of isotonic tetanic contractions with those observed during isotonic twitches in dog gastrocnemius-plantaris muscle. Tetanic contractions (1/s, 200-ms trains of 50 impulses/s) elicited a peak VO2 of 9.01 +/- 0.42 mumol.g-1.min-1, which declined 29% in 30 min. The peak was significantly lower during 4/s twitches (6.23 +/- 0.36 mumol.g-1.min-1), but the rate of decline was similar. Peak blood flow (Q) was 37% higher and decreased more slowly during tetanic than twitch contractions. VO2/Q and VO2/venous PO2 were similar in both groups at peak VO2 and later declined or remained constant over time. Power was significantly greater with tetanic contractions with the relative decline between 3 and 30 min similar in both groups (32 and 37%). In conclusion, tetanic contractions result in significantly higher VO2 and power than do twitch contractions. This was derived primarily from increased Q because the arteriovenous O2 difference was similar. A significant determinant of the difference in Q between twitch and tetanic contractions is mechanical hindrance of Q. There is relatively more time for unhindered flow in the tetanic contractions. In electrically stimulated muscles, maximal VO2 is related to Q and reflects mainly Q through the muscle rather than the VO2 capacity of the muscle.

Fatigue of mammalian skeletal muscle in situ during repetitive contractions.

When the gastrocnemius-plantaris muscle group of the dog is stimulated to contract repetitively for 30 min at frequencies high enough to generate VO2 levels at or near VO2 max, VO2 and mechanical performance decline with time. This decline with time is fatigue, and it occurs during twitch and tetanic contractions that are isometric or isotonic. There is oxidation of the mitochondrial electron transport system, and net lactic acid output is transient, ending after 20 min of contractions. Energy and substrate stores and intracellular pH are only moderately changed and do not appear to be well correlated with the development of fatigue. Blood flow through the muscle is well correlated with the development of fatigue and decreases as fatigue develops in a manner that keeps the blood arteriovenous O2 difference nearly constant. Changing the blood flow alters the rate of development of fatigue as an inverse relation, and this response does not appear to be related to changes in the availability of O2 in the mitochondria. Nerve-muscle transmission of excitation does not seem to be involved in the development of fatigue. Excitation-contraction coupling is well accepted to be at least part of the genesis of the development of fatigue. Metabolic limitations and control may affect excitation-contraction coupling by one or more changes in the internal environment. Blood flow affects this system by an unknown mechanism. The role of blood flow in fatigue deserves further consideration.

Effects of ischemic and hypoxic hypoxia on VO2 and lactic acid output during tetanic contractions.

We measured O2 uptake (VO2), CO2 output (VCO2), and net lactic acid output (L) during a 30-min period of repetitive 1/s isotonic tetanic contractions of the dog gastrocnemius-plantaris muscle group. The conditions were modest ischemic hypoxia (ischemia), hypoxia hypoxia (hypoxia), and free-flow normoxia (control). The major goal was to assess the effects of these perturbations on L during contractions. Ischemia and hypoxia were initiated just before the start of the contractions and at minute 7 of contractions in separate groups of experiments. Whenever applied, both ischemia and hypoxia reduced VO2 compared with the control values. When ischemia was initiated at the start of contractions, L was reduced transiently compared with the controls. When ischemia began at minute 7, L was increased modestly but transiently compared with the controls. When hypoxia was initiated at the start of contractions, L was increased during the entire period of contractions. The L pattern was the same as in the controls, rising to a maximal value at 3 min and declining steadily to a lower value at 30 min. When hypoxia began at minute 7, L declined initially at a slower rate than it did in the controls and was thereby elevated above the controls from 9 to 30 min. Ischemia was associated with a more rapid reduction in mechanical performance than hypoxia. The data suggest that the mechanisms of the decreased mechanical performance and VO2 are different for ischemia and hypoxia.

Oxidation/reduction state of cytochrome oxidase during repetitive contractions.

There is disagreement regarding whether inadequate O2 determines maximal O2 uptake (VO2max) and lactic acid output (L) during muscular activity. Direct assessment of mitochondrial cytochrome oxidase (cytochrome a-a3) oxidation/reduction (O/R) state should provide an unequivocal answer for this issue. A new near-infrared spectrophotometric method was used to measure the O/R state of cytochrome a-a3 of dog gastrocnemius-plantaris muscle in situ during repetitive isotonic twitch and tetanic contractions. Three contraction frequencies were used for each contraction type in alternating sequence to provide a wide range of VO2 up to VO2max. VO2 and L were measured after 3 and 9 min of a 10-min contraction period, and 15 min were allowed for recovery between contraction periods. VO2 increased with contraction frequency. L was variably increased with contraction frequency at 3 min and uptake usually occurred at 9 min, except at the highest tetanic frequency. The O/R span of cytochrome a-a3 was determined by respiring the animals with 100% N2 to determine the most reduced state. This was followed by respiration with 100% O2, which gave the most oxidized state transiently during recovery. Within this span in muscles at rest, cytochrome a-a3 was 50-80% oxidized. During contractions of both types at all frequencies, cytochrome a-a3 always became more oxidized by an additional 10-20%. These findings should put to rest any arguments that inadequate O2 is a determinant of VO2max or L under the conditions of these experiments: repetitive contractions with free flow in self-perfused muscles and normoxia.

Roles of CO2, O2, and acid in arteriovenous [H+] difference during muscle contractions.

To determine the origins of the arteriovenous [H+] difference of muscle during contractions, arterial and muscle venous blood sample pairs were taken before and after 0.5, 5.0, and 30.0 min of 4/s isometric twitches of the gastrocnemius-plantaris muscle group of anesthetized dogs. These samples were analyzed for PO2, PCO2, and pH, the concentrations of O2, CO2, K+, Na+, La-, and Cl- in whole blood, and La-, K+, Na+, and Cl- in plasma. Whole blood was hemolyzed and analyzed for PO2, PCO2, and pH. Net O2 uptake, CO2 output, L, K+, Na+, and Cl- were calculated in addition to net output of non-CO2 acid (HA) and strong ion difference ([SID]) and common ion [SID] ([K+] + [Na+] - [Cl-] - [La-]). From these data we partitioned the origins of the arteriovenous [H+] difference via the common PCO2-pH diagram and via a [H+]-PCO2 diagram and determined whether true plasma arteriovenous [H+] differences reflect plasma and cell arteriovenous [H+] differences. The arteriovenous [H+] differences of plasma and hemolyzed blood were the same, showing that true plasma does reflect plasma and cells. K+ showed a small significant but transient output. Na+ was not significant, whereas Cl- showed a significant transient uptake. Lactate output and HA, calculated for dog blood acid-base, showed transient outputs and were the same. At 5.0 min when the arteriovenous difference was largest, CO2 alone would have increased [H+] 15.9 nmol/l whereas desaturation of Hb would have decreased [H+] 4.2 nmol/l and lactate could have raised [H+] 1.0 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Maximal blood flow and power output of dog muscle in situ.

The two goals of this study were: 1) to establish a stimulation pattern which would drive the gastrocnemius-plantaris muscle of the dog, in situ, to maximal work rate, W, and 2) to determine whether the surgical isolation of the circulation of this muscle, necessary to measure the muscle flow, Q, reduced the muscle's performance. The first goal was achieved in a preparation with minimal surgery, MS, to isolate the nerve and the tendon. The nerve was cut and connected to a stimulator, and the tendon was cut and connected to a pneumatic lever system. Wmax during 1.s-1 contractions occurred with a load of 270 g.g-1 and 200-ms trains of impulses at a frequency of 60.s-1. At 50 imp.s-1, the accepted maximal frequency which would occur in vivo, the Wmax which was maintained for 4 min was 19 mW.g-1. The second goal was met in a second series of experiments in which the venous circulation was isolated, FS. During a 20-min series of 30-s work periods with 2 min rest each, maximal W was 11.9 mW.g-1 at 50 imp.s-1. Following a 10-min additional rest, the muscle was stimulated for 10 min. The W, Q, and VO2 at 2-4 min were 10.0 mW.g-1, 1.73 ml.g-1.min-1 and 194 microliters.g-1.min-1, respectively. Q and VO2 were linearly related to W. Assuming a linear extrapolation, the FS early maximum in the brief tests as W = 11.9 mW.g-1, Q would be 2.06 ml.g-1.min-1 and VO2 would be 231 microliters.g-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

A pictographic essay on blood and tissue oxygen transport.

This review describes the transport of oxygen from ambient air to mitochondria in the cells. Using simple equations and diagrams, the presentation illustrates the variables which determine the magnitude of each of the three major steps in the partial pressure of O2 along the passage, from: (i) ambient air to alveolar gas; (ii) arterial blood to venous blood; and (iii) capillary blood to tissue. The emphasis is on steps (ii) and (iii), and how they are modified from the normoxic case by ischemia, anemia, hypoxia, and increased VO2. The basic context of step (iii) is the Krogh model. This model, despite its limitations, is proposed as conceptually useful in analyzing whole-body or tissue O2 transport.

Effects of adrenergic agonists and antagonists on muscle O2 uptake and lactate metabolism.

To investigate adrenergic receptor-mediated responses in dog gastrocnemius-plantaris muscle, several catecholamine agonists, isoproterenol, epinephrine, norepinephrine, and phenylephrine, and two antagonists, propranolol and phenoxybenzamine, were given during repetitive, isotonic, tetanic contractions. The response variables that were measured were muscle blood flow, shortening during constant load contractions, and arterial and venous O2 and lactate concentrations. The calculated variables were O2 uptake (VO2), net lactic acid output (L), and power output. In the control experiments, the contractions increased VO2 to approximately 50 times rest by 2 min. Thereafter, shortening, work, and VO2 declined together by 17% at 30 min, indicating muscle fatigue. L increased rapidly to nearly 0.8 mumol X g-1 X min-1 by 2 min, declined to 0.3-0.4 mumol X g-1 X min-1 by 7 min, and was like rest at 15, 22.5, and 30 min. The arterial lactate concentration rose steadily from rest to 30 min of contractions. Epinephrine infusion stopped the decline of VO2 during the contractions, but this effect was not observed with the other agonists. Propranolol decreased VO2 compared with controls at 22.5 and 30 min of contractions. Phenoxybenzamine decreased VO2 compared with controls at all times during contraction, and the decline with time was present. Coinfusion of epinephrine with propranolol reduced the decline in VO2 observed with propranolol alone. Both epinephrine and isoproterenol increased L compared with controls. This epinephrine response was antagonized by propranolol but enhanced by phenoxybenzamine. Both isoproterenol and epinephrine infusions increased arterial lactate concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactic acid output of cat gastrocnemius-plantaris during repetitive twitch contractions.

Because fatigable, white (FF) muscle fibers have been reported to have a greater glycolytic capacity and a lower oxidative capacity than fatigue-resistant, red (FR and SR) muscle fibers, it is generally supposed that FF muscle fibers produce and therefore release more lactic acid into the blood during contractions than FR and SR muscle fibers. To test this supposition, the net lactic acid output, L, and O2 uptake, VO2, were measured for the cat gastrocnemius-plantaris muscle during repetitive isometric contractions. The results obtained from this low metabolic capacity (FF, FR and SR muscles) were compared to results obtained previously in the high metabolic capacity (FR and SR muscles) of the same muscle group in the dog during similar contractions. Preliminary studies established that 1 twitch X 2 s-1 provided a similar VO2 pattern during the contractions of cat muscle as 4 twitches X s-1 produced in the dog muscle. The decline in VO2 over a 30-min period of contractions was 12 to 18%, as developed tension declined with fatigue. Thus, the contractions of the cat muscles were matched with the dog muscles in terms of the relative aerobic capacity and development of fatigue. During the 1 twitch X 2 s-1 twitches, the VO2 reached 24.4 +/- 1.41 (SE) microliter X g-1 X min-1 at 10 min of contractions. The VO2 declined to 21.3 +/- 2.3 microliter X g-1 X min-1 by 30 min. The VO2 and tension developed changed parallel to each other. The net L reached 0.21 +/- 0.06 mumol X g-1 X min-1 at 10 min and fell to 0.13 +/- 0.05 mumol X g-1 X min by 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical and physiological bases for lactate production.

I have proposed an explanation of lactic acid production and output by red and white skeletal muscle during repetitive contractions. The proposal does not require O2 lack to slow oxidative phosphorylation. In this proposal lactic acid production is due to the fact that activation of glycolysis is more rapid than activation of oxidative phosphorylation. This results in a transient elevation of NADH in the cytoplasm and net lactic acid production. Once oxidative phosphorylation is fully activated and the activation of glycolysis wanes, balance is again achieved. Lactic acid production decreases and may become net utilization.