Lactate extraction during net lactate release in legs of humans during exercise

Lactate metabolism was studied in six normal males using a primed continuous infusion of lactate tracer during continuous graded supine cycle ergometer exercise. Subjects exercised at 49, 98, 147, and 196 W for 6 min at each work load. Blood was sampled from the brachial artery, the iliac vein, and the brachial vein. Arteriovenous differences were determined for chemical lactate concentration and L-[1-14C]-lactate. Tracer-measured lactate extraction was determined from the decrease in lactate radioactivity per volume of blood perfusing the tissue bed. Net lactate release was determined from the change in lactate concentration across the tissue bed. Total lactate release was taken as the sum of tracer-measured lactate extraction and net (chemical) release. At rest the arms and legs showed tracer-measured lactate extraction, as determined from the isotope extraction, despite net chemical release. Exercise elicited an increase in both net lactate release and tracer-measured lactate extraction by the legs. For the legs the total lactate release (net lactate release + tracer-measured lactate extraction) was roughly equal to twice the net lactate release under all conditions. The tracer-measured lactate extraction by the exercising legs was positively correlated to arterial lactate concentration (r = 0.81, P less than 0.001) at the lower two power outputs. The arms showed net lactate extraction during exercise, which was correlated to the arterial concentration (r = 0.86). The results demonstrate that exercising skeletal muscle extracts a significant amount of lactate during net lactate release and that the working skeletal muscle appears to be a major site of blood lactate removal during exercise.     

Leg glucose and protein metabolism during an acute bout of resistance exercise in humans.

The present study investigated the responses of leg glucose and protein metabolism during an acute bout of resistance exercise. Seven subjects (5 men, 2 women) were studied at rest and during a strenuous lower body resistance exercise regimen consisting of approximately 8 sets of 10 repetitions of leg press at approximately 75% 1 repetition maximum and 8 sets of 8 repetitions of knee extensions at approximately 80% 1 repetition maximum. L-[ring-2H5]phenylalanine was infused throughout the study for measurement of phenylalanine rates of appearance, disappearance, protein synthesis, and protein breakdown across the leg. Femoral arterial and venous blood samples were collected at rest and during exercise for determination of leg blood flow, concentrations of glucose, lactate, alanine, glutamine, glutamate, leucine, and phenylalanine, and phenylalanine enrichments. Muscle biopsies were obtained at rest and immediately after exercise. Leg blood flow was nearly three times (P <0.009) higher and glucose uptake more than five times higher (P=0.009) during exercise than at rest. Leg lactate release was 86 times higher than rest during the exercise bout. Although whole body phenylalanine rate of appearance, an indicator of whole body protein breakdown, was reduced during exercise; leg phenylalanine rate of appearance, rate of disappearance, protein synthesis, and protein breakdown did not change. Arterial and venous alanine concentrations and glutamate uptake were significantly higher during exercise than at rest. We conclude that lower body resistance exercise potently stimulates leg glucose uptake and lactate release. In addition, muscle protein synthesis is not elevated during a bout of resistance exercise.     

Short-term training attenuates muscle TCA cycle expansion during exercise in women.

Muscle glycogenolytic flux and lactate accumulation during exercise are lower after 3-7 days of "short-term" aerobic training (STT) in men (e.g., Green HJ, Helyar R, Ball-Burnett M, Kowalchuk N, Symon S, and Farrance B. J Appl Physiol 72: 484-491, 1992). We hypothesized that 5 days of STT would attenuate pyruvate production and the increase in muscle tricarboxylic acid cycle intermediates (TCAI) during exercise, because of reduced flux through the reaction catalyzed by alanine aminotransferase (AAT; pyruvate + glutamate <--> 2-oxoglutarate + alanine). Eight women [22 +/- 1 yr, peak oxygen uptake (Vo2 peak) = 40.3 +/- 4.6 ml. kg-1. min-1] performed seven 45-min bouts of cycle exercise at 70% Vo2 peak over 9 days (1 bout/day; rest only on days 2 and 8). During the first and last bouts, biopsies (vastus lateralis) were obtained at rest and after 5 and 45 min of exercise. Muscle glycogen concentration was approximately 50% higher at rest after STT (493 +/- 38 vs. 330 +/- 20 mmol/kg dry wt; P 相似文献   

Muscle accounts for glucose disposal but not blood lactate appearance during exercise after acclimatization to 4,300 m.

We hypothesized that the increased blood glucose disappearance (Rd) observed during exercise and after acclimatization to high altitude (4,300 m) could be attributed to net glucose uptake (G) by the legs and that the increased arterial lactate concentration and rate of appearance (Ra) on arrival at altitude and subsequent decrease with acclimatization were caused by changes in net muscle lactate release (L). To evaluate these hypotheses, seven healthy males [23 +/- 2 (SE) yr, 72.2 +/- 1.6 kg], on a controlled diet were studied in the postabsorptive condition at sea level, on acute exposure to 4,300 m, and after 3 wk of acclimatization to 4,300 m. Subjects received a primed-continuous infusion of [6,6-D2]glucose (Brooks et al., J. Appl. Physiol. 70: 919-927, 1991) and [3-13C]lactate (Brooks et al., J. Appl. Physiol. 71:333-341, 1991) and rested for a minimum of 90 min, followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the sea level peak O2 uptake (65 +/- 2% of both acute altitude and acclimatization peak O2 uptake). Glucose and lactate arteriovenous differences across the legs and arms and leg blood flow were measured. Leg G increased during exercise compared with rest, at altitude compared with sea level, and after acclimatization. Leg G accounted for 27-36% of Rd at rest and essentially all glucose Rd during exercise. A shunting of the blood glucose flux to active muscle during exercise at altitude is indicated. With acute altitude exposure, at 5 min of exercise L was elevated compared with sea level or after acclimatization, but from 15 to 45 min of exercise the pattern and magnitude of L from the legs varied and followed neither the pattern nor the magnitude of responses in arterial lactate concentration or Ra. Leg L accounted for 6-65% of lactate Ra at rest and 17-63% during exercise, but the percent Ra from L was not affected by altitude. Tracer-measured lactate extraction by legs accounted for 10-25% of lactate Rd at rest and 31-83% during exercise. Arms released lactate under all conditions except during exercise with acute exposure to high altitude, when the arms consumed lactate. Both active and inactive muscle beds demonstrated simultaneous lactate extraction and release. We conclude that active skeletal muscle is the predominant site of glucose disposal during exercise and at high altitude but not the sole source of blood lactate during exercise at sea level or high altitude.     

MCA Vmean and the arterial lactate-to-pyruvate ratio correlate during rhythmic handgrip.

Regulation of cerebral blood flow during physiological activation including exercise remains unknown but may be related to the arterial lactate-to-pyruvate (L/P) ratio. We evaluated whether an exercise-induced increase in middle cerebral artery mean velocity (MCA Vmean) relates to the arterial L/P ratio at two plasma lactate levels. MCA Vmean was determined by ultrasound Doppler sonography at rest, during 10 min of rhythmic handgrip exercise at approximately 65% of maximal voluntary contraction force, and during 20 min of recovery in seven healthy male volunteers during control and a approximately 15 mmol/l hyperglycemic clamp. Cerebral arteriovenous differences for metabolites were obtained by brachial artery and retrograde jugular venous catheterization. Control resting arterial lactate was 0.78 +/- 0.09 mmol/l (mean +/- SE) and pyruvate 55.7 +/- 12.0 micromol/l (L/P ratio 16.4 +/- 1.0) with a corresponding MCA Vmean of 46.7 +/- 4.5 cm/s. During rhythmic handgrip the increase in MCA Vmean to 51.2 +/- 4.6 cm/s was related to the increased L/P ratio (23.8 +/- 2.5; r2 = 0.79; P < 0.01). Hyperglycemia increased arterial lactate and pyruvate to 1.9 +/- 0.2 mmol/l and 115 +/- 4 micromol/l, respectively, but it did not significantly influence the L/P ratio or MCA Vmean at rest or during exercise. Conversely, MCA Vmean did not correlate significantly, neither to the arterial lactate nor to the pyruvate concentrations. These results support that the arterial plasma L/P ratio modulates cerebral blood flow during cerebral activation independently from the plasma glucose concentration.     

Splanchnic and muscle fructose metabolism during and after exercise

Regional substrate exchange was studied in 12 healthy males during 90 min of bicycle exercise at 30% of maximal O2 consumption with a 20-min recovery. Six subjects received an intravenous fructose infusion (8.5 mmol/min) from 40 min of exercise to the end of recovery. Splanchnic glucose output, muscle glucose uptake, arterial glucose, and insulin were uninfluenced by the infusion. The respiratory exchange ratio rose to 0.93 +/- 0.04, and arterial free fatty acids fell by 50% (P less than 0.05). Fructose was taken up by splanchnic tissues (45% of administered load), leg muscle (28%), and resting muscle (28%). During infusion, arterial lactate and pyruvate rose two- to threefold, and these substrates were released from splanchnic tissues and taken up by exercising and resting muscle. Splanchnic release of lactate, pyruvate, and glucose accounted for 78% of fructose uptake at 90 min of exercise. Uptake of fructose, lactate, and pyruvate accounted for 55% and together with glucose for 103% of the total oxidative metabolism by exercising muscle. The regional fructose uptakes and lactate exchanges persisted throughout recovery. The present results indicate that fructose infusion during leg exercise 1) results in increased carbohydrate oxidation from fructose, lactate, and pyruvate in exercising muscle, 2) exerts a glycogenic effect in resting muscle and liver during exercise and in liver and muscle recovering from exercise, and 3) does not interfere with glucose metabolism, and that fructose transport into muscle differs from that of glucose.     

Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids.

During prolonged exercise, carbohydrate oxidation may result from decreased pyruvate production and increased fatty acid supply and ultimately lead to reduced pyruvate dehydrogenase (PDH) activity. Pyruvate also interacts with the amino acids alanine, glutamine, and glutamate, whereby the decline in pyruvate production could affect tricarboxycylic acid cycle flux as well as gluconeogenesis. To enhance our understanding of these interactions, we studied the time course of changes in substrate utilization in six men who cycled at 44+/-1% peak oxygen consumption (mean+/-SE) until exhaustion (exhaustion at 3 h 23 min+/-11 min). Femoral arterial and venous blood, blood flow measurements, and muscle samples were obtained hourly during exercise and recovery (3 h). Carbohydrate oxidation peaked at 30 min of exercise and subsequently decreased for the remainder of the exercise bout (P<0.05). PDH activity peaked at 2 h of exercise, whereas pyruvate production peaked at 1 h of exercise and was reduced (approximately 30%) thereafter, suggesting that pyruvate availability primarily accounted for reduced carbohydrate oxidation. Increased free fatty acid uptake (P<0.05) was also associated with decreasing PDH activity (P<0.05) and increased PDH kinase 4 mRNA (P<0.05) during exercise and recovery. At 1 h of exercise, pyruvate production was greatest and was closely linked to glutamate, which was the predominant amino acid taken up during exercise and recovery. Alanine and glutamine were also associated with pyruvate metabolism, and they comprised approximately 68% of total amino-acid release during exercise and recovery. Thus reduced pyruvate production was primarily associated with reduced carbohydrate oxidation, whereas the greatest production of pyruvate was related to glutamate, glutamine, and alanine metabolism in early exercise.     

Hyperoxia decreases muscle glycogenolysis, lactate production, and lactate efflux during steady-state exercise

The aim of this study was to determine whether the decreased muscle and blood lactate during exercise with hyperoxia (60% inspired O2) vs. room air is due to decreased muscle glycogenolysis, leading to decreased pyruvate and lactate production and efflux. We measured pyruvate oxidation via PDH, muscle pyruvate and lactate accumulation, and lactate and pyruvate efflux to estimate total pyruvate and lactate production during exercise. We hypothesized that 60% O2 would decrease muscle glycogenolysis, resulting in decreased pyruvate and lactate contents, leading to decreased muscle pyruvate and lactate release with no change in PDH activity. Seven active male subjects cycled for 40 min at 70% VO2 peak on two occasions when breathing 21 or 60% O2. Arterial and femoral venous blood samples and blood flow measurements were obtained throughout exercise, and muscle biopsies were taken at rest and after 10, 20, and 40 min of exercise. Hyperoxia had no effect on leg O2 delivery, O2 uptake, or RQ during exercise. Muscle glycogenolysis was reduced by 16% with hyperoxia (267 +/- 19 vs. 317 +/- 21 mmol/kg dry wt), translating into a significant, 15% reduction in total pyruvate production over the 40-min exercise period. Decreased pyruvate production during hyperoxia had no effect on PDH activity (pyruvate oxidation) but significantly decreased lactate accumulation (60%: 22.6 +/- 6.4 vs. 21%: 31.3 +/- 8.7 mmol/kg dry wt), lactate efflux, and total lactate production over 40 min of cycling. Decreased glycogenolysis in hyperoxia was related to an approximately 44% lower epinephrine concentration and an attenuated accumulation of potent phosphorylase activators ADPf and AMPf during exercise. Greater phosphorylation potential during hyperoxia was related to a significantly diminished rate of PCr utilization. The tighter metabolic match between pyruvate production and oxidation resulted in a decrease in total lactate production and efflux over 40 min of exercise during hyperoxia.     

Leg and arm lactate and substrate kinetics during exercise

To study the role of muscle mass and muscle activity on lactate and energy kinetics during exercise, whole body and limb lactate, glucose, and fatty acid fluxes were determined in six elite cross-country skiers during roller-skiing for 40 min with the diagonal stride (Continuous Arm + Leg) followed by 10 min of double poling and diagonal stride at 72-76% maximal O(2) uptake. A high lactate appearance rate (R(a), 184 +/- 17 micromol x kg(-1) x min(-1)) but a low arterial lactate concentration ( approximately 2.5 mmol/l) were observed during Continuous Arm + Leg despite a substantial net lactate release by the arm of approximately 2.1 mmol/min, which was balanced by a similar net lactate uptake by the leg. Whole body and limb lactate oxidation during Continuous Arm + Leg was approximately 45% at rest and approximately 95% of disappearance rate and limb lactate uptake, respectively. Limb lactate kinetics changed multiple times when exercise mode was changed. Whole body glucose and glycerol turnover was unchanged during the different skiing modes; however, limb net glucose uptake changed severalfold. In conclusion, the arterial lactate concentration can be maintained at a relatively low level despite high lactate R(a) during exercise with a large muscle mass because of the large capacity of active skeletal muscle to take up lactate, which is tightly correlated with lactate delivery. The limb lactate uptake during exercise is oxidized at rates far above resting oxygen consumption, implying that lactate uptake and subsequent oxidation are also dependent on an elevated metabolic rate. The relative contribution of whole body and limb lactate oxidation is between 20 and 30% of total carbohydrate oxidation at rest and during exercise under the various conditions. Skeletal muscle can change its limb net glucose uptake severalfold within minutes, causing a redistribution of the available glucose because whole body glucose turnover was unchanged.     

Effect of increased plasma free fatty acid concentrations on muscle metabolism in exercising men

The effect of increasing plasma concentrations of free fatty acids on substrate utilization in muscle during exercise was investigated in 11 healthy young males. One hour of dynamic knee extension at 80% of knee-extensor maximal work capacity was performed first with one leg and then with the other leg during infusion of Intralipid and heparin. Substrate utilization was assessed from arterial and femoral venous blood sampling as well as from muscle biopsies. Intralipid infusion increased mean plasma free fatty acid concentrations from 0.54 +/- 0.08 to 1.12 +/- 0.09 (SE) mM. Thigh glucose uptake during rest, exercise, and recovery was decreased by 64, 33, and 42%, respectively, by Intralipid, whereas muscle glycogen breakdown and release of lactate, pyruvate, and citrate were unaffected. Concentrations of glucose, glucose 6-phosphate, and lactate in muscle before and at termination of exercise were unaffected by Intralipid. During exercise, net leg uptake of plasma free fatty acids was not measurably increased by Intralipid, whereas uptake of ketone bodies was. Local respiratory quotient across the leg was not changed by Intralipid (control 0.87 +/- 0.02, Intralipid 0.86 +/- 0.02). Arterial concentrations of insulin, norepinephrine, and epinephrine were similar in the two trials. It is concluded that at rest and during exercise at a moderate intensity (requiring approximately equal contributions from fat and carbohydrate metabolism), muscle carbohydrate metabolism is affected only with regard to uptake of glucose when plasma concentrations of lipid and lipid metabolites are increased. This effect may be by direct inhibition of glucose transport rather than by the classic glucose-fatty acid cycle.     

Alanine and glutamine synthesis and release from skeletal muscle. I. Glycolysis and amino acid release.

The synthesis and release of alanine and glutamine were investigated with an intact rat epitrochlaris muscle preparation. This preparation will maintain on incubation for up to 6 hours, tissue levels of phosphocreatine, ATP, ADP, lactate, and pyruvate closely approximating those values observed in gastrocnemius muscles freeze-clamped in vivo. The epitrochlaris preparation releases amino acids in the same relative proportions and amounts as a perfused rat hindquarter preparation and human skeletal muscle. Since amino acids were released during incubation without observable changes in tissue amino acids levels, rates of alanine and glutamine release closely approximate net amino acid synthesis. Large increases in either glucose uptake or glycolysis in muscle were not accompanied by changes in either alanine or glutamine synthesis. Insulin increased muscle glucose uptake 4-fold, but was without effect on alanine and glutamine release. Inhibition of glycolysis by iodacetate did not decrease the rate of alanine synthesis. The rates of alanine and glutamine synthesis and release from muscle decreased significantly during prolonged incubation despite a constant rate of glucose uptake and pyruvate production. Alanine synthesis and release were decreased by aminooxyacetic acid, an inhibitor of alanine aminotransferase. This inhibition was accompanied by a compensatory increase in the release of other amino acids, such as aspartate, an amino acid which was not otherwise released in appreciable quantities by muscle. The release of alanine, pyruvate, glutamate, and glutamine were observed to be interrelated events, reflecting a probable near-equilibrium state of alanine aminotransferase in skeletal muscle. It is concluded that glucose metabolism and amino acid release are functionally independent processes in skeletal muscle. Alanine release reflects the de novo synthesis of the amino acid and does not arise from the selective proteolysis of an alanine-rich storage protein. It appears that the rate of alanine and glutamine synthesis in skeletal muscle is dependent upon the transformation and metabolism of amino acid precursors.     

Decreased exercise muscle lactate release after high altitude acclimatization

Blood lactate concentration during exercise decreases after acclimatization to high altitude, but it is not clear whether there is decreased lactate release from the exercising muscle or if other mechanisms are involved. We measured iliac venous and femoral arterial lactate concentrations and iliac venous blood flow during cycle exercise before and after acclimatization to 4,300 m. During hypoxia, at a given O2 consumption the venous and arterial lactate concentrations, the venous and arterial concentration differences, and the net lactate release were lower after acclimatization than during acute altitude exposure. While breathing O2-enriched air after acclimatization at a given O2 consumption the venous and arterial lactate concentrations and the venous and arterial concentration differences were significantly lower, and the net lactate release tended to be lower than while breathing ambient air at sea level before acclimatization. We conclude that the lower lactate concentration in venous and arterial blood during exercise after altitude acclimatization reflected less net release of lactate by the exercising muscles, and that this likely resulted from the acclimatization process itself rather than the hypoxia per se.     

Similar carbohydrate but enhanced lactate utilization during exercise after 9 wk of acclimatization to 5,620 m

We hypothesized that reliance on lactate as a means of energy distribution is higher after a prolonged period of acclimatization (9 wk) than it is at sea level due to a higher lactate Ra and disposal from active skeletal muscle. To evaluate this hypothesis, six Danish lowlanders (25 +/- 2 yr) were studied at rest and during 20 min of bicycle exercise at 146 W at sea level (SL) and after 9 wk of acclimatization to 5,260 m (Alt). Whole body glucose Ra was similar at SL and Alt at rest and during exercise. Lactate Ra was also similar for the two conditions at rest; however, during exercise, lactate Ra was substantially lower at SL (65 micro mol. min(-1). kg body wt(-1)) than it was at Alt (150 micro mol. min(-1). kg body wt(-1)) at the same exercise intensity. During exercise, net lactate release was approximately 6-fold at Alt compared with SL, and related to this, tracer-calculated leg lactate uptake and release were both 3- or 4-fold higher at Alt compared with SL. The contribution of the two legs to glucose disposal was similar at SL and Alt; however, the contribution of the two legs to lactate Ra was significantly lower at rest and during exercise at SL (27 and 81%) than it was at Alt (45 and 123%). In conclusion, at rest and during exercise at the same absolute workload, CHO and blood glucose utilization were similar at SL and at Alt. Leg net lactate release was severalfold higher, and the contribution of leg lactate release to whole body lactate Ra was higher at Alt compared with SL. During exercise, the relative contribution of lactate oxidation to whole body CHO oxidation was substantially higher at Alt compared with SL as a result of increased uptake and subsequent oxidation of lactate by the active skeletal muscles.     

Supramaximal exercise after training-induced hypervolemia. II. Blood/muscle substrates and metabolites

Blood and muscle substrates and metabolites were investigated in six healthy males (ranging in age from 19 to 23 yr) during three consecutive days of supramaximal exercise training. Muscle biopsies from the vastus lateralis and arterialized blood samples from a hand vein were extracted before the exercise and at selected times during the intermittent (1 min work to 4 min rest) cycling. The results indicated that blood glucose concentration was significantly depressed (P less than 0.05) on both days 2 and 3 of the training, whereas plasma free fatty acids and blood glycerol, pyruvate, alanine, and lactate were unaffected. At the muscle level, glucose and lactate concentrations were depressed on days 2 and 3, whereas ATP and glycogen were reduced only on the final day of training. No training-induced alterations were noted for muscle glucose 6-phosphate or muscle ADP. These results indicate that the approximate 10-11% reduction in O2-carrying capacity accompanying the short-term training does not directly and negatively influence muscle energy metabolism during the exercise. Rather, the explanation for the altered muscle and blood constituents must be sought from other effects of the training such as impaired carbohydrate repletion.     

Glucose metabolism in perfused skeletal muscle. Effects of starvation, diabetes, fatty acids, acetoacetate, insulin and exercise on glucose uptake and disposition.

1. The regulation of glucose uptake and disposition in skeletal muscle was studied in the isolated perfused rat hindquarter. 2. Insulin and exercise, induced by sciatic-nerve stimulation, enhanced glucose uptake about tenfold in fed and starved rats, but were without effect in rats with diabetic ketoacidosis. 3. At rest, the oxidation of lactate (0.44 mumol/min per 30 g muscle in fed rats) was decreased by 75% in both starved and diabetic rats, whereas the release of alanine and lactate (0.41 and 1.35 mumol/min per 30 g respectively in the fed state) was increased. Glycolysis, defined as the sum of lactate+alanine release and lactate oxidation, was not decreased in either starvation or diabetes. 4. In all groups, exercise tripled O2 consumption (from approximately 8 to approximately 25 mumol/min per 30 g of muscle) and increased the release and oxidation of lactate five- to ten-fold. The differences in lactate release between fed, starved and diabetic rats observed at rest were no longer apparent; however, lactate oxidation was still several times greater in the fed group. 5. Perfusion of the hindquarter of a fed rat with palmitate, octanoate or acetoacetate did not alter glucose uptake or lactate release in either resting or exercising muslce; however, lactate oxidation was significantly inhibited by acetoacetate, which also increased the intracellular concentration of acetyl-CoA. 6. The data suggest that neither that neither glycolysis nor the capacity for glucose transport are inhbitied in the perfused hindquarter during starvation or perfusion with fatty acids or ketone bodies. On the other hand, lactate oxidation is inhibited, suggesting diminished activity of pyruvate dehydrogenase. 7. Differences in the regulation of glucose metabolism in heart and skeletal muscle and the role of the glucose/fatty acid cycle in each tissue are discussed.     

Effects of adenosine, exercise, and moderate acute hypoxia on energy substrate utilization of human skeletal muscle

Glucose metabolism increases in hypoxia and can be influenced by endogenous adenosine, but the role of adenosine for regulating glucose metabolism at rest or during exercise in hypoxia has not been elucidated in humans. We studied the effects of exogenous adenosine on human skeletal muscle glucose uptake and other blood energy substrates [free fatty acid (FFA) and lactate] by infusing adenosine into the femoral artery in nine healthy young men. The role of endogenous adenosine was studied by intra-arterial adenosine receptor inhibition (aminophylline) during dynamic one-leg knee extension exercise in normoxia and acute hypoxia corresponding to ～3,400 m of altitude. Extraction and release of energy substrates were studied by arterial-to-venous (A-V) blood samples, and total uptake or release was determined by the product of A-V differences and muscle nutritive perfusion measured by positron emission tomography. The results showed that glucose uptake increased from a baseline value of 0.2 ± 0.2 to 2.0 ± 2.2 μmol·100 g(-1)·min(-1) during adenosine infusion (P < 0.05) at rest. Although acute hypoxia enhanced arterial FFA levels, it did not affect muscle substrate utilization at rest. During exercise, glucose uptake was higher (195%) during acute hypoxia compared with normoxia (P = 0.058), and aminophylline had no effect on energy substrate utilization during exercise, despite that arterial FFA levels were increased. In conclusion, exogenous adenosine at rest and acute moderate hypoxia during low-intensity knee-extension exercise increases skeletal muscle glucose uptake, but the increase in hypoxia appears not to be mediated by adenosine.     

Effect of respiratory acidosis on metabolism in exercise

Five healthy males took part in two separate studies. In one study subjects breathed air (control, C) and in the other 5% CO2 in 21% O2 (respiratory acidosis, RA). Measurements were made at rest, during exercise at 30 and 60% maximal O2 uptake (VO2 max), (20 min each) and in recovery. RA was associated with higher arterial CO2 partial pressure (PCO2) and bicarbonate and lower pH than C. The increase with exercise in plasma lactate (mmol . l-1) was less in RA than C from 1.0 +/- 0.15 (SE) (C = 1.1 +/- 0.17) at rest to 5.3 +/- 1.25 (C = 6.8 +/- 0.98) at 60% VO2 max (P less than 0.10). Plasma pyruvate, alanine, and glycerol concentrations increased with exercise; free fatty acids did not change. There were no significant differences between RA and C in any of these metabolites. Norepinephrine concentrations were similar at rest but increased to a greater extent during exercise in RA than C (P less than 0.02). Epinephrine levels were also higher in RA than C at 60% VO2 max (NS); the two subjects in whom lactate was not lower with RA showed the greatest increase in epinephrine. Exercise in RA was associated with higher heart rates (P less than 0.05), blood pressures (NS), and ventilation (P less than 0.01). In hypercapnia the metabolic effects of acidosis are modified by increased levels of circulating catecholamines.     

Effects of hyperoxia on skeletal muscle carbohydrate metabolism during transient and steady-state exercise.

This study compared the effects of inspiring either a hyperoxic (60% O(2)) or normoxic gas (21% O(2)) while cycling at 70% peak O(2) uptake on 1) the ATP derived from substrate phosphorylation during the initial minute of exercise, as estimated from phosphocreatine degradation and lactate accumulation, and 2) the reliance on carbohydrate utilization and oxidation during steady-state cycling, as estimated from net muscle glycogen use and the activity of pyruvate dehydrogenase (PDH) in the active form (PDH(a)), respectively. We hypothesized that 60% O(2) would decrease substrate phosphorylation at the onset of exercise and that it would not affect steady-state exercise PDH activity, and therefore muscle carbohydrate oxidation would be unaltered. Ten active male subjects cycled for 15 min on two occasions while inspiring 21% or 60% O(2), balance N(2). Blood was obtained throughout and skeletal muscle biopsies were sampled at rest and 1 and 15 min of exercise in each trial. The ATP derived from substrate-level phosphorylation during the initial minute of exercise was unaffected by hyperoxia (21%: 52.2 +/- 11.1; 60%: 54.0 +/- 9.5 mmol ATP/kg dry wt). Net glycogen breakdown during 15 min of cycling was reduced during the 60% O(2) trial vs. 21% O(2) (192.7 +/- 25.3 vs. 138.6 +/- 16.8 mmol glycosyl units/kg dry wt). Hyperoxia had no effect on PDH(a), because it was similar to the 21% O(2) trial at rest and during exercise (21%: 2.20 +/- 0.26; 60%: 2.25 +/- 0.30 mmol.kg wet wt(-1).min(-1)). Blood lactate was lower (6.4 +/- 1.0 vs. 8.9 +/- 1.0 mM) at 15 min of exercise and net muscle lactate accumulation was reduced from 1 to 15 min of exercise in the 60% O(2) trial compared with 21% (8.6 +/- 5.1 vs. 27.3 +/- 5.8 mmol/kg dry wt). We concluded that O(2) availability did not limit oxidative phosphorylation in the initial minute of the normoxic trial, because substrate phosphorylation was unaffected by hyperoxia. Muscle glycogenolysis was reduced by hyperoxia during steady-state exercise, but carbohydrate oxidation (PDH(a)) was unaffected. This closer match between pyruvate production and oxidation during hyperoxia resulted in decreased muscle and blood lactate accumulation. The mechanism responsible for the decreased muscle glycogenolysis during hyperoxia in the present study is not clear.     

Alanine metabolism in skeletal muscle in tissue culture.

Alanine production by skeletal muscle in tissue culture was studied using an established myogenic line (L6) of rat skeletal muscle cells. Correlation analyses were performed on rates of metabolism of alanine, glucose, lactate and pyruvate over incubation periods up to 96 h. Alanine production did not correlate significantly with glucose utilization (r = 0.24, P less than 0.20). Alanine production, however, did correlate with lactate production (r = 0.72, P less than 0.0005) as well as medium (r = 0.50, P less than 0.025) and intracellular (r = 0.85, P less than 0.0005) pyruvate concentrations. The intercepts of the latter two correlation analyses indicated that when medium or cell pyruvate fell below 0.28 mM or 1 nmol/mg protein, respectively, net alanine consumption occurred. Alanine synthesis also correlated (r = 0.71, P less than 0.0005) with the percent change in the cell mass action ratio for the sum of the alanine and aspartate aminotransferase reactions, i.e., [alanine] [malate]/[aspartate] [lactate]. These results suggest that alanine production is not necessarily linked to the rate of glucose utilization but rater to pyruvate overflow above a critical intracellular level; under conditions of pyruvate overflow, alanine synthesis is driven by the tendency to establish equilibrium between metabolites of the linked amino acid transaminases in skeletal muscle.     

Effects of acetazolamide on metabolic and respiratory responses to exercise at maximal O2 uptake

Changes in blood gases, ions, lactate, pH, hemoglobin, blood temperature, total body metabolism, and muscle metabolites were measured before and during exercise (except muscle), at fatigue, and during recovery in normal and acetazolamide-treated horses to test the hypothesis that an acetazolamide-induced acidosis would compromise the metabolism of the horse exercising at maximal O2 uptake. Acetazolamide-treated horses had a 13-mmol/l base deficit at rest, higher arterial Po2 at rest and during exercise, higher arterial and mixed venous Pco2 during exercise, and a 48-s reduction in run time. Arterial pH was lower during exercise but not in recovery after acetazolamide. Blood temperature responses were unaffected by acetazolamide administration. O2 uptake was similar during exercise and recovery after acetazolamide treatment, whereas CO2 production was lower during exercise. Muscle [glycogen] and pH were lower at rest, whereas heart rate, muscle pH and [lactate], and plasma [lactate] and [K+] were lower and plasma [Cl-] higher following exercise after acetazolamide treatment. These data demonstrate that acetazolamide treatment aggravates the CO2 retention and acidosis occurring in the horse during heavy exercise. This could negatively affect muscle metabolism and exercise capacity.