Lactate removal is not enhanced in nonstimulated perfused skeletal muscle after endurance training.

The effects of endurance training (running 40 m/min grade for 60 min, 5 days/wk for 8 wk) on skeletal muscle lactate removal was studied in rats by utilizing the isolated hindlimb perfusion technique. Hindlimbs were perfused (single-pass) with Krebs-Henseleit bicarbonate buffer, fresh bovine erythrocytes (hematocrit approximately 30%), 10 mM lactate, and [U-14C]lactate (30,000 dpm/ml). Arterial and venous blood samples were collected every 10 min for the duration of the experiment to assess lactate uptake. During perfusions, no significant differences in skeletal muscle lactate uptake were observed between trained (7.31 +/- 0.20 micromol/min) and control hindlimbs (6.98 +/- 0.43 micromol/min). In support, no significant differences were observed for [14C]lactate uptake in trained (22,776 +/- 370 dpm/min) compared with control hindlimbs (21,924 +/- 1,373 dpm/min). Concomitant with these observations, no significant differences were observed between groups for oxygen consumption (4.93 +/- 0.18 vs. 4.92 +/- 0.13 micromol/min), net skeletal muscle glycogen synthesis (7.1 +/- 0.4 vs. 6.5 +/- 0.3 micromol x 40 min(-1) x g(-1)), or 14CO2 production (2,203 +/- 185 vs. 2,098 +/- 155 dpm/min), trained and control, respectively. These findings indicate that endurance training does not affect lactate uptake or alter the metabolic fate of lactate in quiescent skeletal muscle.     

Disposal of blood [1-13C]lactate in humans during rest and exercise

Lactate irreversible disposal (RiLa) and oxidation (RoxLa) rates were studied in six male subjects during rest (Re), easy exercise [EE, 140 min of cycling at 50% of maximum O2 consumption (VO2max)] and hard exercise (HE, 65 min at 75% VO2max). Twenty minutes into each condition, subjects received a Na+-L(+)-[1-13C]lactate intravenous bolus injection. Blood was sampled intermittently from the contralateral arm for metabolite levels, acid-base status, and enrichment of 13C in lactate. Expired air was monitored continuously for determination of respiratory parameters, and aliquots were collected for determination of 13C enrichment in CO2. Steady-rate values for O2 consumption (VO2) were 0.33 +/- 0.01, 2.11 +/- 0.03, and 3.10 +/- 0.03 l/min for Re, EE, and HE, respectively. Corresponding values of blood lactate levels were 0.84 +/- 0.01, 1.33 +/- 0.05, and 4.75 +/- 0.28 mM in the three conditions. Blood lactate disposal rates were significantly correlated to VO2 (r = 0.78), averaging 123.4 +/- 20.7, 245.5 +/- 40.3, and 316.2 +/- 53.7 mg X kg-1 X h-1 during Re, EE, and HE, respectively. Lactate oxidation rate was also linearly related to VO2 (r = 0.81), and the percentage of RiLa oxidized increased from 49.3% at rest to 87.0% during exercise. A curvilinear relationship was found between RiLa and blood lactate concentration. It was concluded that, in humans, 1) lactate disposal (turnover) rate is directly related to the metabolic rate, 2) oxidation is the major fate of lactate removal during exercise, and 3) blood lactate concentration is not an accurate indicator of lactate disposal and oxidation.     

Altered cardiac metabolic phenotype after prolonged inhibition of NO synthesis in chronically instrumented dogs

Acute inhibition of nitric oxide (NO) synthase causes a reversible alteration in myocardial substrate metabolism. We tested the hypothesis that prolonged NO synthase inhibition alters cardiac metabolic phenotype. Seven chronically instrumented dogs were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, 35 mg.kg(-1).day(-1) po) for 10 days to inhibit NO synthesis, and seven were used as controls. Cardiac free fatty acid, glucose, and lactate oxidation were measured by infusion of [(3)H]oleate, [(14)C]glucose, and [(13)C]lactate, respectively. After 10 days of L-NAME administration, despite no differences in left ventricular afterload, cardiac O(2) consumption was significantly increased by 30%, consistent with a marked enhancement in baseline oxidation of glucose (6.9 +/- 2.0 vs. 1.7 +/- 0.5 micromol.min(-1).100 g(-1), P < 0.05 vs. control) and lactate (21.6 +/- 5.6 vs. 11.8 +/- 2.6 micromol.min(-1).100 g(-1), P < 0.05 vs. control). When left ventricular afterload was increased by ANG II infusion to stimulate myocardial metabolism, glucose oxidation was augmented further in the L-NAME than in the control group, whereas free fatty acid oxidation decreased. Exogenous NO (diethylamine nonoate, 0.01 micromol.kg(-1).min(-1) iv) could not reverse this metabolic alteration. Consistent with the accelerated rate of carbohydrate oxidation, total myocardial pyruvate dehydrogenase activity and protein expression were higher (38 and 34%, respectively) in the L-NAME than in the control group. Also, protein expression of the constitutively active glucose transporter GLUT-1 was significantly elevated (46%) vs. control. We conclude that prolonged NO deficiency causes a profound alteration in cardiac metabolic phenotype, characterized by selective potentiation of carbohydrate oxidation, that cannot be reversed by a short-term infusion of exogenous NO. This phenomenon may constitute an adaptive mechanism to counterbalance cardiac mechanical inefficiency.     

V(O2) max is unaffected by altering the temporal pattern of stimulation frequency in rat hindlimb in situ.

It might be anticipated that fatiguing contractions would impair the aerobic metabolic response in skeletal muscle if significant fatigue developed before full activation of aerobic metabolism. On the basis of this premise, we examined two groups of rats to test the hypothesis that a gradual increase in stimulation frequency would yield a higher maximal O2 uptake (Vo2 max) than beginning immediately with an intense stimulation frequency because of a slower progression of fatigue under the former conditions. In one group of animals, the distal hindlimb muscles were electrically stimulated at a frequency of 60 tetani/min for 4 min (F60; n = 6 rats); in the other group, the muscles were incrementally stimulated for 1 min at each of 7.5, 15, 30, and 60 tetani/min and for 2 min at 90 tetani/min (FInc; n = 5 rats). Despite large differences in rate of fatigue [time to 60% of initial force was 47 +/- 3 (SE) vs. 188 +/- 1 s in F60 and FInc, respectively] and the time at which Vo2 max occurred (120 +/- 15 vs. 264 +/- 6 s), Vo2 max was not different (419 +/- 24 vs. 381 +/- 44 micromol x min-1. 100 g-1). Furthermore, time x tension integral at Vo2 max (3.82 +/- 0.41 vs. 4.07 +/- 0.31 N. s) and peak lactate efflux (910 +/- 45 vs. 800 +/- 98 micromol x min-1. 100 g-1) were not different between groups. Thus our results show that the more rapid progression of fatigue in F60 did not compromise the aerobic metabolic response in electrically stimulated rat hindlimb muscles. However, in both groups, O2 uptake and lactate efflux declined after Vo2 max was attained in similar proportion to a further fall in force, suggesting that ongoing fatigue with intense contractions reduced ATP demand below that requiring maximal aerobic and glycolytic metabolic responses once Vo2 max was reached.     

Net lactate uptake during progressive steady-level contractions in canine skeletal muscle

The purpose of this study was to determine the changes in net lactate uptake (L) by skeletal muscle with a constant elevated blood lactate concentration during steady-level contractions of increasing intensity. The gastrocnemius-plantaris muscle group was isolated in situ in 11 anesthetized dogs. An infusion of lactate/lactic acid at a pH of 3.5-3.7 established a blood lactate concentration of approximately 9 mM while maintaining normal blood gas/pH status. L was measured during three consecutive 30-min periods during which the muscles 1) rested, 2) contracted at 1 Hz, and 3) contracted at 4 Hz. L was always positive, indicating net uptake throughout the lactate/lactic acid infusion. Steady-level O2 uptake averaged 10.9 +/- 2.2 ml.kg-1.min-1 (0.49 +/- 0.10 mmol.kg-1.min-1) at rest, 39.3 +/- 2.1 (1.75 +/- 0.09) at 1 Hz, and 127.8 +/- 9.2 (5.70 +/- 0.41) at 4 Hz. Steady-level L increased with the metabolic rate from 0.113 +/- 0.058 mmol.kg-1.min-1 at rest to 0.329 +/- 0.026 at 1 Hz and 0.715 +/- 0.108 at 4 Hz. The increase in L from rest to 1 Hz was accomplished mainly by an increase in arteriovenous lactate difference, whereas the increase from 1 to 4 Hz was entirely due to a large increase in blood flow. These results support the idea that skeletal muscle is not simply a producer of lactate but can be a significant consumer of lactate even during contractions with a large elevation in metabolic rate.     

Effect of acidosis on skeletal muscle metabolism with and without propranolol

Does the stimulatory effect of circulating catecholamines counteract the inhibitory effect of acidosis on skeletal muscle metabolism? To investigate this possibility, we studied gastrocnemii in dogs breathing either air (n = 10) or 4% carbon dioxide in air (n = 10) at rest and during contractions. In five dogs from each group, we infused propranolol into the arterial supply of the right and left muscles for 40 min. After 30 min of infusion, the left muscle was stimulated at 3 Hz for 10 min. During the 10th min of contractions, we removed and froze both muscles in liquid nitrogen. Oxygen uptake and blood flow to the left muscle prior to or during stimulation was not affected by acidosis either with or without propranolol. Glycogen concentration in resting muscle was unaffected by acidosis with or without propranolol. There was an acidosis related decrease of approximately 50% in the glycolytic intermediates (glucose 6-phosphate, fructose 1,6-diphosphate, alpha-glycerol phosphate, and dihydroxyacetone phosphate) in unstimulated muscles without beta-blockade. At rest, acidosis decreased muscle lactate by 50% with and 64% without propranolol, but lactate release was decreased only with acidosis without propranolol (1.4-0.1 mumols/kg.s). Acidosis without propranolol had no effect on the changes in glycogen concentration or the change in the concentration of glycolytic intermediates resulting from contractions. In beta-blocked muscle, the difference between stimulated and unstimulated concentrations of glycogen and glycolytic intermediates including lactate was 20-50% smaller with acidosis. Thus, with beta-blockade, the acidotic effects at rest disappeared and an inhibition of the metabolic adjustment to contractions appeared, indicating that circulating catecholamines do modify some metabolic effects of acidosis.     

Recovery from short term intense exercise: its relation to capillary supply and blood lactate concentration

Muscle force recovery from short term intense exercise was examined in 16 physically active men. They performed 50 consecutive maximal voluntary knee extensions. Following a 40-s rest period five additional maximal contractions were executed. The decrease in torque during the 50 contractions and the peak torque during the five contractions relative to initial torque were used as indices for fatigue and recovery, respectively. Venous blood samples were collected repeatedly up to 8 min post exercise for subsequent lactate analyses. Muscle biopsies were obtained from m. vastus lateralis and analysed for fiber type composition, fiber area, and capillary density. Peak torque decreased 67 (range 47-82%) as a result of the repeated contractions. Following recovery, peak torque averaged 70 (47-86%) of the initial value. Lactate concentration after the 50 contractions was 2.9 +/- 1.3 mmol X 1(-1) and the peak post exercise value averaged 8.7 +/- 2.1 mmol X 1(-1). Fatigue and recovery respectively were correlated with capillary density (r = -0.71 and 0.69) but not with fiber type distribution. A relationship was demonstrated between capillary density and post exercise/peak post exercise blood lactate concentration (r = 0.64). Based on the present findings it is suggested that lactate elimination from the exercising muscle is partly dependent upon the capillary supply and subsequently influences the rate of muscle force recovery.     

Brain oxygen utilization is unchanged by hypoglycemia in normal humans: lactate, alanine, and leucine uptake are not sufficient to offset energy deficit

During hypoglycemia, substrates other than glucose have been suggested to serve as alternate neural fuels. We evaluated brain uptake of endogenously produced lactate, alanine, and leucine at euglycemia and during insulin-induced hypoglycemia in 17 normal subjects. Cross-brain arteriovenous differences for plasma glucose, lactate, alanine, leucine, and oxygen content were quantitated. Cerebral blood flow (CBF) was measured by Fick methodology using N(2)O as the dilution indicator gas. Substrate uptake was measured as the product of CBF and the arteriovenous concentration difference. As arterial glucose concentration fell, cerebral oxygen utilization and CBF remained unchanged. Brain glucose uptake (BGU) decreased from 36.3+/-2.6 to 26.6+/-2.1 micromol.100 g of brain(-1).min(-1) (P<0.001), equivalent to a drop in ATP of 291 micromol.100 g(-1).min(-1). Arterial lactate rose (P<0.001), whereas arterial alanine and leucine fell (P<0.009 and P<0.001, respectively). Brain lactate uptake (BLU) increased from a net release of -1.8+/- 0.6 to a net uptake of 2.5+/-1.2 micromol.100 g(-1).min(-1) (P<0.001), equivalent to an increase in ATP of 74 micromol.100 g(-1).min(-1). Brain leucine uptake decreased from 7.1+/-1.2 to 2.5 +/- 0.5 micromol.100 g(-1).min(-1) (P<0.001), and brain alanine uptake trended downward (P<0.08). We conclude that the ATP generated from the physiological increase in BLU during hypoglycemia accounts for no more than 25% of the brain glucose energy deficit.     

Pyruvate shuttling during rest and exercise before and after endurance training in men.

We describe the isotopic exchange of lactate and pyruvate after arm vein infusion of [3-(13)C]lactate in men during rest and exercise. We tested the hypothesis that working muscle (limb net lactate and pyruvate exchange) is the source of the elevated systemic lactate-to-pyruvate concentration ratio (L/P) during exercise. We also hypothesized that the isotopic equilibration between lactate and pyruvate would decrease in arterial blood as glycolytic flux, as determined by relative exercise intensity, increased. Nine men were studied at rest and during exercise before and after 9 wk of endurance training. Although during exercise arterial pyruvate concentration decreased to below rest values (P < 0.05), pyruvate net release from working muscle was as large as lactate net release under all exercise conditions. Exogenous (arterial) lactate was the predominant origin of pyruvate released from working muscle. With no significant effect of exercise intensity or training, arterial isotopic equilibration [(IE(pyruvate)/IE(lactate)).100%, where IE is isotopic enrichment] decreased significantly (P < 0.05) from 60 +/- 3.1% at rest to an average value of 12 +/- 2.7% during exercise, and there were no changes in femoral venous isotopic equilibration. These data show that 1). the isotopic equilibration between lactate and pyruvate in arterial blood decreases significantly during exercise; 2). working muscle is not solely responsible for the decreased arterial isotopic equilibration or elevated arterial L/P occurring during exercise; 3). working muscle releases similar amounts of lactate and pyruvate, the predominant source of the latter being arterial lactate; 4). pyruvate clearance from blood occurs extensively outside of working muscle; and 5). working muscle also releases alanine, but alanine release is an order of magnitude smaller than lactate or pyruvate release. These results portray the complexity of metabolic integration among diverse tissue beds in vivo.     

Plasma glucose kinetics during prolonged exercise in trained humans when fed carbohydrate

Nine endurance-trained men exercised on a cycle ergometer at approximately 68% peak O2 uptake to the point of volitional fatigue [232 +/- 14 (SE) min] while ingesting an 8% carbohydrate solution to determine how high glucose disposal could increase under physiological conditions. Plasma glucose kinetics were measured using a primed, continuous infusion of [6,6-2H]glucose and the appearance of ingested glucose, assessed from [3-3H]glucose that had been added to the carbohydrate drink. Plasma glucose was increased (P < 0.05) after 30 min of exercise but thereafter remained at the preexercise level. Glucose appearance rate (R(a)) increased throughout exercise, reaching its peak value of 118 +/- 7 micromol. kg(-1). min(-1) at fatigue, whereas gut R(a) increased continuously during exercise, peaking at 105 +/- 10 micromol. kg(-1). min(-1) at the point of fatigue. In contrast, liver glucose output never rose above resting levels at any time during exercise. Glucose disposal (R(d)) increased throughout exercise, reaching a peak value of 118 +/- 7 micromol. kg(-1). min(-1) at fatigue. If we assume 95% oxidation of glucose R(d), estimated exogenous glucose oxidation at fatigue was 1.36 +/- 0.08 g/min. The results of this study demonstrate that glucose uptake increases continuously during prolonged, strenuous exercise when carbohydrate is ingested and does not appear to limit exercise performance.     

Red blood cell lactate transport in sickle disease and sickle cell trait.

This study determined and compared rates and mechanisms of lactate transport in red blood cells (RBCs) of persons with 1) sickle cell disease (HbSS), 2) sickle cell trait (HbAS), and 3) a control group (HbAA). Blood samples were drawn from 30 African-American volunteers (10 HbSS, 10 HbAS, 10 HbAA). Lactate influx into RBCs was measured by using [14C]lactate at six (2, 5, 10, 15, 25, and 40 mM) unlabeled lactate concentrations. The monocarboxylate transporter pathway was blocked by p-chloromercuriphenylsulfonic acid to determine its percent contribution to total lactate influx. Generally, total lactate influx into RBCs from the HbSS group was significantly greater than influx into RBCs from HbAS or HbAA, with no difference between HbAS and HbAA. Faster influx into HbSS RBCs was attributed to increased monocarboxylate transporter activity [increased apparent Vmax (V'max)]. V'max (4.7 +/- 0.6 micromol x ml(-1) x min(-1)) for HbSS RBCs was significantly greater than V'max of HbAS RBCs (2.9 +/- 1.5 micromol x ml(-1) x min(-1)) and HbAA RBCs (2.0 +/- 0.5 micromol x ml(-1) x min(-1)). Km (42.8 +/- 8 mM) for HbSS RBCs was significantly greater than Km (27 +/- 12 mM) for HbAA RBCs. We suspect that elevated erythropoietin levels in response to chronic anemia and/or pharmacological treatment (erythropoietin injections, hydroxyurea ingestion) is the underlying mechanism for increased lactate transport capacity in HbSS RBCs.     

Metabolic response to carbohydrate ingestion during exercise in males and females

The present study investigated potential sex-related differences in the metabolic response to carbohydrate (CHO) ingestion during exercise. Moderately endurance-trained men and women (n = 8 for each sex) performed 2 h of cycling at approximately 67% Vo(2 max) with water (WAT) or CHO ingestion (1.5 g of glucose/min). Substrate oxidation and kinetics were quantified during exercise using indirect calorimetry and stable isotope techniques ([(13)C]glucose ingestion, [6,6-(2)H(2)]glucose, and [(2)H(5)]glycerol infusion). In both sexes, CHO ingestion significantly increased the rates of appearance (R(a)) and disappearance (R(d)) of glucose during exercise compared with WAT ingestion [males: WAT, approximately 28-29 micromol x kg lean body mass (LBM)(-1) x min(-1); CHO, approximately 53 micromol x kg LBM(-1) x min(-1); females: WAT, approximately 28-29 micromol x kg LBM(-1) x min(-1); CHO, approximately 61 micromol x kg LBM(-1) x min(-1); main effect of trial, P < 0.05]. The contribution of plasma glucose oxidation to the energy yield was significantly increased with CHO ingestion in both sexes (from approximately 10% to approximately 20% of energy expenditure; main effect of trial, P < 0.05). Liver-derived glucose oxidation was reduced, although the rate of muscle glycogen oxidation was unaffected with CHO ingestion (males: WAT, 108 +/- 12 micromol x kg LBM(-1) x min(-1); CHO, 108 +/- 11 micromol x kg LBM(-1) x min(-1); females: WAT, 89 +/- 10 micromol x kg LBM(-1) x min(-1); CHO, 93 +/- 11 micromol x kg LBM(-1) x min(-1)). CHO ingestion reduced fat oxidation and lipolytic rate (R(a) glycerol) to a similar extent in both sexes. Finally, ingested CHO was oxidized at similar rates in men and women during exercise (peak rates of 0.70 +/- 0.08 and 0.65 +/- 0.06 g/min, respectively). The present investigation suggests that the metabolic response to CHO ingestion during exercise is largely similar in men and women.     

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.     

Lactate as substrate for glycogen resynthesis after exercise

Muscle glycogen levels in the perfused rat hemicorpus preparation were reduced two-thirds by electrical stimulation plus exposure to epinephrine (10(-7) M) for 30 min. During the contraction period muscle lactate concentrations increased from a control level of 3.6 +/- 0.6 to a final value of 24.1 +/- 1.6 mumol/g muscle. To determine whether the lactate that had accumulated in muscle during contraction could be used to resynthesize glycogen, glycogen levels were determined after 1-3 h of recovery from the contraction period during which time the perfusion medium (flow-through system) contained low (1.3 mmol/l) or high (10.5 or 18 mmol/l) lactate concentrations but no glucose. With the low perfusate lactate concentration, muscle lactate levels declined to 7.2 +/- 0.8 mumol/g muscle by 3 h after the contraction period and muscle glycogen levels did not increase (1.28 +/- 0.07 at 3 h vs. 1.35 +/- 0.09 mg glucosyl U/g at end of exercise). Lactate disappearance from muscle was accounted for entirely by output into the venous effluent. With the high perfusate lactate concentrations, muscle lactate levels remained high (13.7 +/- 1.7 and 19.3 +/- 2.0 mumol/g) and glycogen levels increased by 1.11 and 0.86 mg glucosyl U/g, respectively, after 1 h of recovery from exercise. No more glycogen was synthesized when the recovery period was extended. Therefore, it appears that limited resynthesis of glycogen from lactate can occur after the contraction period but only when arterial lactate concentrations are high; otherwise the lactate that builds up in muscle during contraction will diffuse into the bloodstream.     

Skeletal muscle metabolism is unaffected by DCA infusion and hyperoxia after onset of intense aerobic exercise

This study investigated whether hyperoxic breathing (100% O(2)) or increasing oxidative substrate supply [dichloroacetate (DCA) infusion] would increase oxidative phosphorylation and reduce the reliance on substrate phosphorylation at the onset of high-intensity aerobic exercise. Eight male subjects cycled at 90% maximal O(2) uptake (VO(2 max)) for 90 s in three randomized conditions: 1) normoxic breathing and saline infusion over 1 h immediately before exercise (CON), 2) normoxic breathing and saline infusion with DCA (100 mg/kg body wt), and 3) hyperoxic breathing for 20 min at rest and during exercise and saline infusion (HYP). Muscle biopsies from the vastus lateralis were sampled at rest and after 30 and 90 s of exercise. DCA infusion increased pyruvate dehydrogenase (PDH) activation above CON and HYP (3.10 +/- 0.23, 0.56 +/- 0.08, 0.69 +/- 0.05 mmol x kg wet muscle(-1) x min(-1), respectively) and significantly increased both acetyl-CoA and acetylcarnitine (11.0 +/- 0.7, 2.0 +/- 0.5, 2.2 +/- 0.5 mmol/kg dry muscle, respectively) at rest. However, DCA and HYP did not alter phosphocreatine degradation and lactate accumulation and, therefore, the reliance on substrate phosphorylation during 30 s (CON, 51.2 +/- 5.4; DCA, 56.5 +/- 7.1; HYP, 69.5 +/- 6.3 mmol ATP/kg dry muscle) and 90 s of exercise (CON, 90.6 +/- 9.5; DCA, 107.2 +/- 13.0; HYP, 101.2 +/- 15.2 mmol ATP/kg dry muscle). These data suggest that the rate of oxidative phosphorylation at the onset of exercise at 90% VO(2 max) is not limited by oxygen availability to the active muscle or by substrate availability (metabolic inertia) at the level of PDH in aerobically trained subjects.     

Kinetics of intramuscular triglyceride fatty acids in exercising humans.

A pulse ([(14)C]palmitate)-chase ([(3)H]palmitate) approach was used to study intramuscular triglyceride (imTG) fatty acid and plasma free fatty acid (FFA) kinetics during exercise at approximately 45% peak O(2) consumption in 12 adults. Vastus lateralis muscle was biopsied before and after 90 min of bicycle exercise; (3)H(2)O production, breath (14)CO(2) excretion and lipid oxidation (indirect calorimetry) rates were measured during exercise. Results: during exercise, 8.2+/-1.2 and 8.4+/-0.7 micromol x kg(-1) x min(-1) of imTG fatty acids and plasma FFA, respectively, were oxidized according to isotopic measurements. The sum of these two values was not different (P = 0.6) from lipid oxidation by indirect calorimetry (15.4 +/-1.6 micromol x kg(-1) x min(-1)); the isotopic and indirect calorimetry values were correlated (r = 0.79, P<0.005). During exercise, imTG turnover rate was 0.32+/-0.07%/min (6.0+/-2.0 micromol of imTG x kg wet muscle(-1) x min(-1)) and plasma FFA were incorporated into imTG at a rate of 0.7+/-0.1 micromol x kg wet muscle(-1) x min(-1). The imTG pool size did not change during exercise. This pulse-chase, dual tracer appears to be a reasonable approach to measure oxidation and synthesis kinetics of imTG.     

Effect of lactate infusion on M-wave characteristics and force in the rat plantaris muscle during repeated stimulation in situ.

It is unclear whether accumulation of lactate in skeletal muscle during exercise contributes to muscle fatigue. The purpose of the present study was to examine the effect of lactate infusion on muscle fatigue during prolonged indirect stimulation in situ. For this purpose, the plantaris muscle was electrically stimulated (50 Hz, for 200 ms, every 2.7 s, 5 V) in situ through the sciatic nerve to perform concentric contractions for 60 min while either saline or lactate was infused intravenously (8 rats/group). Lactate infusion (lactate concentration approximately 12 mM) attenuated the reduction in submaximal dynamic force (-49 vs. -68% in rats infused with saline; P < 0.05). Maximum dynamic and isometric forces at the end of the period of stimulation were also higher (P < 0.05) in rats infused with lactate (3.8 +/- 0.3 and 4.4 +/- 0.3 N) compared with saline (3.1 +/- 0.2 and 3.6 +/- 0.2 N). The beneficial effect of lactate infusion on muscle force during prolonged stimulation was associated with a better maintenance of M-wave characteristics compared with control. In contrast, lactate infusion was not associated with any reduction in muscle glycogen utilization or with any reduction of fatigue at the neuromuscular junction (as assessed through maximal direct muscle stimulation: 200 Hz, 200 ms, 150 V).     

Preexercise medium-chain triglyceride ingestion does not alter muscle glycogen use during exercise.

This investigation determined whether ingestion of a tolerable amount of medium-chain triglycerides (MCT; approximately 25 g) reduces the rate of muscle glycogen use during high-intensity exercise. On two occasions, seven well-trained men cycled for 30 min at 84% maximal O(2) uptake. Exactly 1 h before exercise, they ingested either 1) carbohydrate (CHO; 0.72 g sucrose/kg) or 2) MCT+CHO [0.36 g tricaprin (C10:0)/kg plus 0.72 g sucrose/kg]. The change in glycogen concentration was measured in biopsies taken from the vastus lateralis before and after exercise. Additionally, glycogen oxidation was calculated as the difference between total carbohydrate oxidation and the rate of glucose disappearance from plasma (R(d) glucose), as measured by stable isotope dilution techniques. The change in muscle glycogen concentration was not different during MCT+CHO and CHO (42.0 +/- 4.6 vs. 38.8 +/- 4.0 micromol glucosyl units/g wet wt). Furthermore, calculated glycogen oxidation was also similar (331 +/- 18 vs. 329 +/- 15 micromol. kg(-1). min(-1)). The coingestion of MCT+CHO did increase (P < 0.05) R(d) glucose at rest compared with CHO (26.9 +/- 1.5 vs. 20.7 +/- 0. 7 micromol.kg(-1). min(-1)), yet during exercise R(d) glucose was not different during the two trials. Therefore, the addition of a small amount of MCT to a preexercise CHO meal did not reduce muscle glycogen oxidation during high-intensity exercise, but it did increase glucose uptake at rest.     

Does exercise-induced hypoxemia modify lactate influx into erythrocytes and hemorheological parameters in athletes?

This study investigated 1) red blood cells (RBC) rigidity and 2) lactate influxes into RBCs in endurance-trained athletes with and without exercise-induced hypoxemia (EIH). Nine EIH and six non-EIH subjects performed a submaximal steady-state exercise on a cyclo-ergometer at 60% of maximal aerobic power for 10 min, followed by 15 min at 85% of maximal aerobic power. At rest and at the end of exercise, arterialized blood was sampled for analysis of arterialized pressure in oxygen, and venous blood was drawn for analysis of plasma lactate concentrations and hemorheological parameters. Lactate influxes into RBCs were measured at three labeled [U-14C]lactate concentrations (1.6, 8.1, and 41 mM) on venous blood sampled at rest. The EIH subjects had higher maximal oxygen uptake than non-EIH (P < 0.05). Total lactate influx was significantly higher in RBCs from EIH compared with non-EIH subjects at 8.1 mM (1,498.1 +/- 87.8 vs. 1,035.9 +/- 114.8 nmol.ml(-1).min(-1); P < 0.05) and 41 mM (2,562.0 +/- 145.0 vs. 1,618.1 +/- 149.4 nmol.ml(-1).min(-1); P < 0.01). Monocarboxylate transporter-1-mediated lactate influx was also higher in EIH at 8.1 mM (P < 0.05) and 41 mM (P < 0.01). The drop in arterial oxygen partial pressure was negatively correlated with total lactate influx measured at 8.1 mM (r = -0.82, P < 0.05) and 41 mM (r = -0.84, P < 0.05) in the two groups together. Plasma lactate concentrations and hemorheological data were similar in the two groups at rest and at the end of exercise. The results showed higher monocarboxylate transporter-1-mediated lactate influx in the EIH subjects and suggested that EIH could modify lactate influx into erythrocyte. However, higher lactate influx in EIH subjects was not accompanied by an increase in RBC rigidity.     

Effect of carbohydrate ingestion on glucose kinetics and muscle metabolism during intense endurance exercise.

There has been recent interest in the potential performance and metabolic effects of carbohydrate ingestion during exercise lasting approximately 1 h. In this study, 13 well-trained men ingested in randomized order either a 6% glucose solution (CHO trial) or a placebo (Con trial) during exercise to exhaustion at 83+/-1% peak oxygen uptake. In six subjects, vastus lateralis muscle was sampled at rest, at 32 min, and at exhaustion, and in six subjects, glucose kinetics was determined by infusion of [6,6-(2)H]glucose in both trials and ingestion of [6-(3)H]glucose in the CHO trial. Of the 84 g of glucose ingested during exercise in the CHO trial, only 22 g appeared in the peripheral circulation. This resulted in a small (12 g) but significant (P<0.05) increase in glucose uptake without influencing carbohydrate oxidation, muscle glycogen use, or time to exhaustion (CHO: 68.1+/-4.1 min; Con: 69.6+/-5.5 min). Decreases in muscle phosphocreatine content and increases in muscle inosine monophosphate and lactate content during exercise were similar in the two trials. Although endogenous glucose production during exercise was partially suppressed in the CHO trial, it remained significantly above preexercise levels throughout exercise. In conclusion, only 26% of the ingested glucose appeared in the peripheral circulation. Glucose ingestion increased glucose uptake and partially reduced endogenous glucose production but had no effect on carbohydrate oxidation, muscle metabolism, or time to exhaustion during exercise at 83% peak oxygen uptake.