Muscle interstitial glucose and lactate levels during dynamic exercise in humans determined by microdialysis.

The purpose of the present study was to use the microdialysis technique to determine skeletal muscle interstitial glucose and lactate concentrations during dynamic incremental exercise in humans. Microdialysis probes were inserted into the vastus lateralis muscle, and subjects performed knee extensor exercise at workloads of 10, 20, 30, 40, and 50 W. The in vivo probe recoveries determined at rest by the internal reference method for glucose and lactate were 28.7 +/- 2.5 and 32.0 +/- 2.7%, respectively. As exercise intensity increased, probe recovery also increased, and at the highest workload probe recovery for glucose (61.0 +/- 3.9%) and lactate (66. 3 +/- 3.6%) had more than doubled. At rest the interstitial glucose concentration (3.5 +/- 0.2 mM) was lower than both the arterial (5.6 +/- 0.2 mM) and venous (5.3 +/- 0.3 mM) plasma water glucose levels. The interstitial glucose levels remained lower (P < 0.05) than the arterial and venous plasma water glucose concentrations during exercise at all intensities and at 10, 20, 30, and 50 W, respectively. At rest the interstitial lactate concentration (2.5 +/- 0.2 mM) was higher (P < 0.05) than both the arterial (0.9 +/- 0. 2 mM) and venous (1.1 +/- 0.2 mM) plasma water lactate levels. This relationship was maintained (P < 0.05) during exercise at workloads of 10, 20, and 30 W. These data suggest that interstitial glucose delivery at rest is flow limited and that during exercise changes in the interstitial concentrations of glucose and lactate mirror the changes observed in the venous plasma water compartments. Furthermore, skeletal muscle contraction results in an increase in the diffusion coefficient of glucose and lactate within the interstitial space as reflected by an elevation in probe recovery during exercise.     

alpha 1-Adrenergic-receptor responsiveness in skeletal muscle during dynamic exercise

Attenuation of sympathetic vasoconstriction(sympatholysis) in working muscles during dynamic exercise iscontroversial. One potential mechanism is a reduction in₁-adrenergic-receptorresponsiveness. The purpose of this study was to examine₁-adrenergic-receptor-mediated vasoconstriction in resting and working skeletal muscles by using intra-arterial infusions of a selective agonist. Seven mongrel dogswere instrumented chronically with flow probes on the external iliacarteries of both hindlimbs and a catheter in one femoral artery. Aselective ₁-adrenergic-receptoragonist (phenylephrine) was infused as a bolus into the femoral arterycatheter at rest and during exercise. All dogs ran on amotorized treadmill at two exercise intensities (3 and 6 miles/h).Intra-arterial infusions of the same effective concentration ofphenylephrine elicited reductions in vascular conductance of 76 ± 4, 76 ± 6, and 67 ± 5% (P > 0.05) at rest, 3 miles/h, and 6 miles/h, respectively. Systemic bloodpressure and blood flow in the contralateral iliac artery wereunaffected by phenylephrine. These results do not demonstrate anattenuation of vasoconstriction to a selective ₁-agonist during exercise anddo not support the concept of sympatholysis.

     

Anabolic signaling and protein synthesis in human skeletal muscle after dynamic shortening or lengthening exercise

We hypothesized a differential activation of the anabolic signaling proteins protein kinase B (PKB) and p70 S6 kinase (p70(S6K)) and subsequent differential stimulation of human muscle protein synthesis (MPS) after dynamic shortening or lengthening exercise. Eight healthy men [25 +/- 5 yr, BMI 26 +/- 3 kg/m(-2) (means +/- SD)] were studied before and after 12 min of repeated stepping up to knee height, and down again, while carrying 25% of their body weight, i.e., shortening exercise with the "up" leg and lengthening exercise with contralateral "down" leg. Quadriceps biopsies were taken before and 3, 6, and 24 h after exercise. After exercise, over 2 h before the biopsies, the subjects ingested 500 ml of water containing 45 g of essential amino acids and 135 g of sucrose. Rates of muscle protein synthesis were determined via incorporation over time of [1-(13)C]leucine (相似文献   

Interstitial pH, K(+), lactate, and phosphate determined with MSNA during exercise in humans

The purpose of the present study was to use the microdialysis technique to simultaneously measure the interstitial concentrations of several putative stimulators of the exercise pressor reflex during 5 min of intermittent static quadriceps exercise in humans (n = 7). Exercise resulted in approximately a threefold (P < 0.05) increase in muscle sympathetic nerve activity (MSNA) and 13 +/- 3 beats/min (P < 0.05) and 20 +/- 2 mmHg (P < 0.05) increases in heart rate and blood pressure, respectively. During recovery, all reflex responses quickly returned to baseline. Interstitial lactate levels were increased (P < 0.05) from rest (1.1 +/- 0.1 mM) to exercise (1. 6 +/- 0.2 mM) and were further increased (P < 0.05) during recovery (2.0 +/- 0.2 mM). Dialysate phosphate concentrations were 0.55 +/- 0. 04, 0.71 +/- 0.05, and 0.48 +/- 0.03 mM during rest, exercise, and recovery, respectively, and were significantly elevated during exercise. At the onset of exercise, dialysate K(+) levels rose rapidly above resting values (4.2 +/- 0.1 meq/l) and continued to increase during the exercise bout. After 5 min of contractions, dialysate K(+) levels had peaked with an increase (P < 0.05) of 0.6 +/- 0.1 meq/l and subsequently decreased during recovery, not being different from rest after 3 min. In contrast, H(+) concentrations rapidly decreased (P < 0.05) from resting levels (69.4 +/- 3.7 nM) during quadriceps exercise and continued to decrease with a mean decline (P < 0.05) of 16.7 +/- 3.8 nM being achieved after 5 min. During recovery, H(+) concentrations rapidly increased and were not significantly different from baseline after 1 min. This study represents the first time that skeletal muscle interstitial pH, K(+), lactate, and phosphate have been measured in conjunction with MSNA, heart rate, and blood pressure during intermittent static quadriceps exercise in humans. These data suggest that interstitial K(+) and phosphate, but not lactate and H(+), may contribute to the stimulation of the exercise pressor reflex.     

Adenine nucleotide degradation in human skeletal muscle during prolonged exercise

Eight healthy men cycled at a work load corresponding to approximately 70% of maximal O2 uptake (VO2max) to fatigue (exercise I). Exercise to fatigue at the same work load was repeated after 75 min of rest (exercise II). Exercise duration averaged 65 and 21 min for exercise I and II, respectively. Muscle (quadriceps femoris) content of glycogen decreased from 492 +/- 27 to 92 +/- 20 (SE) mmol/kg dry wt and from 148 +/- 17 to 56 +/- 17 (SE) mmol/kg dry wt during exercise I and II, respectively. Muscle and blood lactate were only moderately increased during exercise. The total adenine nucleotide pool (TAN = ATP + ADP + AMP) decreased and inosine 5'-monophosphate (IMP) increased in the working muscle during both exercise I (P less than 0.001) and II (P less than 0.01). Muscle content of ammonia (NH3) increased four- and eight-fold during exercise I and II, respectively. The working legs released NH3, and plasma NH3 increased progressively during exercise. The release of NH3 at the end of exercise II was fivefold higher than that at the same time point in exercise I (P less than 0.001, exercise I vs. II). It is concluded that submaximal exercise to fatigue results in a breakdown of the TAN in the working muscle through deamination of AMP to IMP and NH3. The relatively low lactate levels demonstrate that acidosis is not a necessary prerequisite for activation of AMP deaminase. It is suggested that the higher average rate of AMP deamination during exercise II vs. exercise I is due to a relative impairment of ATP resynthesis caused by the low muscle glycogen level.     

Proton efflux in human skeletal muscle during recovery from exercise

In recovery from exercise, phosphocreatine resynthesis results in the net generation of protons, while the net efflux of protons restores pH to resting values. Because proton efflux rate declines as pH increases, it appears to have an approximately linear pH-dependence. We set out to examine this in detail using recovery data from human calf muscle. Proton efflux rates were calculated from changes in pH and phosphocreatine concentration, measured by ³¹P magnetic resonance spectroscopy, after incremental dynamic exercise to exhaustion. Results were collected post hoc into five groups on the basis of end-exercise pH. Proton efflux rates declined approximately exponentially with time. These were rather similar in all groups, even when pH changes were small, so that the apparent rate constant (the ratio of efflux rate to pH change) varied widely. However, all groups showed a consistent pattern of decrease with time; the halftimes of both proton efflux rate and the apparent rate constant were longer at lower pH. At each time-point, proton efflux rates showed a significant pH-dependence [slope 17 (3) mmol · l⁻¹ · min⁻¹ · pH unit⁻¹ at the start of recovery, mean (SEM)], but also a significant intercept at resting pH [16 (3) mmol · l⁻¹ · min⁻¹ at the start of recovery]. The intercept and the slope both decreased with time, with halftimes of 0.37 (0.06) and 1.4 (0.4) min, respectively. We conclude that over a wide range of end-exercise pH, net proton efflux during recovery comprises pH-dependent and pH-independent components, both of which decline with time. Comparison with other data in the literature suggests that lactate/proton cotransport can be only a small component of this initial recovery proton efflux. Accepted: 5 May 1997     

Effects of PDH activation by dichloroacetate in human skeletal muscle during exercise in hypoxia

During the onset of exercise in hypoxia, the increased lactate accumulation is associated with a delayed activation of pyruvate dehydrogenase (PDH; Parolin ML, Spreit LL, Hultman E, Hollidge-Horvat MG, Jones NL, and Heigenhauser GJF. Am J Physiol Endocrinol Metab 278: E522-E534, 2000). The present study investigated whether activation of PDH with dichloroacetate (DCA) before exercise would reduce lactate accumulation during exercise in acute hypoxia by increasing oxidative phosphorylation. Six subjects cycled on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake after a saline (control) or DCA infusion while breathing 11% O(2). Muscle biopsies of the vastus lateralis were taken at rest and after 1 and 15 min of exercise. DCA increased PDH activity at rest and at 1 min of exercise, resulting in increased acetyl-CoA concentration and acetylcarnitine concentration at rest and at 1 min. In the first minute of exercise, there was a trend toward a lower phosphocreatine (PCr) breakdown with DCA compared with control. Glycogenolysis was lower with DCA, resulting in reduced lactate concentration ([lactate]), despite similar phosphorylase a mole fractions and posttransformational regulators. During the subsequent 14 min of exercise, PDH activity was similar, whereas PCr breakdown and muscle [lactate] were reduced with DCA. Glycogenolysis was lower with DCA, despite similar mole fractions of phosphorylase a, and was due to reduced posttransformational regulators. The results from the present study support the hypothesis that lactate production is due in part to metabolic inertia and cannot solely be explained by an oxygen limitation, even under conditions of acute hypoxia.     

Ammonia and amino acid metabolism in human skeletal muscle during exercise.

This review focuses on the ammonia and amino acid metabolic responses of active human skeletal muscle, with a particular emphasis on steady-state exercise. Ammonia production in skeletal muscle involves the purine nucleotide cycle and the amino acids glutamate, glutamine, and alanine and probably also includes the branched chain amino acids as well as aspartate. Ammonia production is greatest during prolonged, steady state exercise that requires 60-80% VO2max and is associated with glutamine and alanine metabolism. Under these circumstances it is unresolved whether the purine nucleotide cycle (AMP deamination) is active; if so, it must be cycling with no IMP accumulation. It is proposed that under these circumstances the ammonia is produced from slow twitch fibers by the deamination of the branched chain amino acids. The ammonia response can be suppressed by increasing the carbohydrate availability and this may be mediated by altering the availability of the branched chain amino acids. The fate of the ammonia released into the circulation is unresolved, but there is indirect evidence that a considerable portion may be excreted by the lung in expired air.     

Regulation of glycogen phosphorylase and PDH during exercise in human skeletal muscle during hypoxia

The present study examined the acute effects of hypoxia on the regulation of skeletal muscle metabolism at rest and during 15 min of submaximal exercise. Subjects exercised on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake while breathing 11% O(2) (hypoxia) or room air (normoxia). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to hypoxia. In the 1st min of exercise, glycogenolysis was significantly greater in hypoxia compared with normoxia. This small difference in glycogenolysis was associated with a tendency toward a greater concentration of substrate, free P(i), in hypoxia compared with normoxia. Pyruvate dehydrogenase activity (PDH(a)) was lower in hypoxia at 1 min compared with normoxia, resulting in a reduced rate of pyruvate oxidation and a greater lactate accumulation. During the last 14 min of exercise, glycogenolysis was greater in hypoxia despite a lower mole fraction of phosphorylase a. The greater glycogenolytic rate was maintained posttransformationally through significantly higher free [AMP] and [P(i)]. At the end of exercise, PDH(a) was greater in hypoxia compared with normoxia, contributing to a greater rate of pyruvate oxidation. Because of the higher glycogenolytic rate in hypoxia, the rate of pyruvate production continued to exceed the rate of pyruvate oxidation, resulting in significant lactate accumulation in hypoxia compared with no further lactate accumulation in normoxia. Hence, the elevated lactate production associated with hypoxia at the same absolute workload could in part be explained by the effects of hypoxia on the activities of the rate-limiting enzymes, phosphorylase and PDH, which regulate the rates of pyruvate production and pyruvate oxidation, respectively.     

Changes in magnetic resonance images in human skeletal muscle after eccentric exercise

To investigate the time-course of changes in transverse relaxation time (T₂) and cross-sectional area (CSA) of the quadriceps muscle after a single session of eccentric exercise, magnetic resonance imaging was performed on six healthy male volunteers before and at 0, 7, 15, 20, 30 and 60 min and 12, 24, 36, 48, 72 and 168 h after exercise. Although there was almost no muscle soreness immediately after exercise, it started to increase 1 day after, peaking 1–2 days after the exercise (P<0.01). Immediately after exercise, T₂ increased significantly in the rectus femoris, vastus lateralis and intermedius muscles (P<0.05) and decreased quickly continuing until 60 min after exercise. At and after the 12th h, a significant increase was perceived again in the T₂ values of the vastus lateralis and intermedius muscles (P<0.01) [maximum 9.3 (SEM 2.8)% and 10.9 (SEM 2.2)%, respectively]. The maximal values were exhibited at 24–36 h after exercise. In contrast, the rectus femoris muscle showed no delayed-stage increase. Also, in CSA, an increase after 12 h was observed in addition to the one immediately after exercise in the vastus lateralis, intermedius and medialis and quadriceps muscles as a whole (P < 0.01), reaching the maximal values at 12–24 h after exercise. The plasma creative kinase activity remained unchanged up to 24 h after and then increased significantly 48 h after exercise (P < 0.05). Beginning 12 h after exercise, the subjects whose T₂ and CSA increased less than the others displayed a faster decrease in muscle soreness. These results suggested that T₂ and CSA displayed bimodal responses after eccentric exercise and the time-courses of changes in them were similar to those in muscle soreness.     

Coexistence of potentiation and low-frequency fatigue during voluntary exercise in human skeletal muscle

The role of muscle potentiation in overcoming low-frequency fatigue (LFF) as it developed during submaximal voluntary exercise was investigated in eight males (age 26.4 +/- 0.7 years, mean +/- SE) performing isometric leg extension at approximately 30% of maximal voluntary contraction for 60 min using a 0.5-duty cycle (1 s contraction, 1 s rest). At 5, 20, 40, and 60 min, exercise was interrupted for 3 min, and the maximum positive rate of force development (+dF/dtmax) and maximal twitch force (Pt) were measured in maximal twitch contractions at 0, 1, 2, and 3 min of rest (R0, R1, R2, R3); they were also measured at 15 min of recovery following the entire 60-min exercise period. These measures were compared with pre-exercise (PRE) as an indicator of potentiation. Force at low frequency (10 Hz) was also measured at R0, R1, R2, and R3, and at 15 min of recovery, while force at high frequency (100 Hz) was measured only at R0 and R3 and in recovery. Voluntary exercise increased twitch +dF/dtmax at R0 following 5, 20, 40, and 60 min of exercise, from 2553 +/- 150 N/s at PRE to 39%, 41%, 42%, and 36% above PRE, respectively (P<0.005). Twitch +dF/dtmax decayed at brief rest (R3) following 20, 40, and 60 min of exercise (P<0.05). Pt at R0 following 5 and 20 min of exercise was above that at PRE (P<0.05), indicating that during the early phase of moderate-intensity repetitive exercise, potentiation occurs in the relative absence of LFF. At 40 and 60 min of exercise, Pt at R0 was unchanged from PRE. The LFF (10 Hz) induced by the protocol was evident at 40 and 60 min (R0-R3; P<0.05) and at 15 min following exercise (P<0.05). High-frequency force was not significantly compromised by the protocol. Since twitch force was maintained, these results suggest that as exercise progresses, LFF develops, which can be compensated for by potentiation.