Lactate disposal in resting trained and untrained forearm skeletal muscle during high intensity leg exercise

Summary At a given oxygen uptake ( O₂) and exercise intensity blood lactate concentrations are lower following endurance training. While decreased production of lactate by trained skeletal muscle is the commonly accepted cause, the contribution from increased lactate removal, comprising both uptake and metabolic disposal, has been less frequently examined. In the present study the role of resting skeletal muscle in the removal of an arterial lactate load (approximately 11 mmol·-l^–1) generated during high intensity supine leg exercise (20 min at approximately 83% maximal oxygen uptake) was compared in the untrained (UT) and trained (T) forearms of five male squash players. Forearm blood flow and the venoarterial lactate concentration gradient were measured and a modified form of the Fick equation used to determine the relative contributions to lactate removal of passive uptake and metabolic disposal. Significant lactate uptake and disposal were observed in both forearms without any change in forearm O₂. Neither the quantity of lactate taken up [UT, 344.2 (SEM 118.8) mol·100 ml^–1; T, 330.3 (SEM 85.3) mol·100 ml^–1] nor the quantity disposed of [UT, 284.0 (SEM 123.3) mol·100 ml^–1, approximately 83% of lactate uptake; T, 300.8 (SEM 77.7) mol·100 ml^–1, approximately 91% of lactate uptake] differed between the two forearms. It is concluded that while significant lactate disposal occurs in resting skeletal muscle during high intensity exercise the lower blood lactate concentrations following endurance training are unlikely to result from an increase in lactate removal by resting trained skeletal muscle.     

Regulation of skeletal muscle perfusion during exercise

For exercise to be sustained, it is essential that adequate blood flow be provided to skeletal muscle. The local vascular control mechanisms involved in regulating muscle perfusion during exercise include metabolic control, endothelium-mediated control, propagated responses, myogenic control, and the muscle pump. The primary determinant of muscle perfusion during sustained exercise is the metabolic rate of the muscle. Metabolites from contracting muscle diffuse to resistance arterioles and act directly to induce vasodilation, or indirectly to inhibit noradrenaline release from sympathetic nerve endings and oppose α-adrenoreceptor-mediated vasoconstriction. The vascular endothelium also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that are prominent in establishing basal vascular tone, but these substances do not appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth muscle cells may also be involved in propagating vasodilator signals along arterioles to parent and daughter vessels. Myogenic autoregulation does not appear to be involved in the exercise hyperemia in muscle, but the rhythmic propulsion of blood from skeletal muscle veins facilitates venous return to the heart and muscle perfusion. It appears that the primary determinants of sustained exercise hyperemia in skeletal muscle are metabolic vasodilation and increased vascular conductance via the muscle pump. Additionally, sympathetic neural control is important in regulating muscle blood flow during exercise.     

NADH in human skeletal muscle during short-term intense exercise

The influence of high-intensity bicycle exercise on the redox level and lactate accumulation in skeletal muscle (m. quadriceps femoris) of man has been investigated. Six subjects exercised to exhaustion at a load corresponding to 100% VO2max. Muscle content of NADH, determined by the bioluminescence technique, increased from (means +/- SEM) 0.089 +/- 0.007 mmol/kg dry wt. at rest to 0.190 +/- 0.031 after 2 min of exercise (P less than 0.05) and to 0.213 +/- 0.021 at exhaustion (P less than 0.05). Values after 2 min exercise and at exhaustion were not statistically different (P greater than 0.05). Muscle lactate was increased 13-fold after 2 min of exercise and 22-fold at exhaustion as compared to the resting value. After 10 min recovery NADH was restored back to the pre-exercise level whereas muscle lactate was still elevated. The increase of muscle NADH during exercise is in contrast to earlier studies on isolated animal muscles, where an oxidation of NADH was observed during contractions. The difference might be due to the experimental model (isolated muscle vs. in vivo) or to the analytical method (qualitative data by reflectance fluorimetri from the surface of intact muscle vs. quantitative data from muscle extracts). Calculations of the cytosolic NADH concentration from the lactate dehydrogenase equilibrium show that 95% or more of the NADH is confined to the mitochondrial compartment. The observed increase of muscle NADH therefore imply that the redox potential of the mitochondria is decreased during intense exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of glycogen synthase in skeletal muscle during exercise

Glycogen synthase (GS) catalyses the incorporation of uridine diphosphate-glucose into glycogen in skeletal muscle. In concert with the glucose transport step, GS activity is thought to be rate-limiting in the disposal of glucose as muscle glycogen. Glycogen synthase is regulated by both allosteric factors (primarily glucose 6-phosphate) and covalent modification by reversible phosphorylation and dephosphorylation leading to inactivation and activation of GS, respectively. Exercise activates both stimulatory and inhibitory regulators of GS and it is thought that the resultant activity of GS during exercise depends on the relative strength of opposing signals. However, the mechanisms by which exercise regulates GS activity are not fully understood. Glycogen breakdown, the GM-protein phosphatase 1 complex and possibly cellular relocalization of GS may be considered important factors involved in the stimulation of GS activity during exercise, while adenosine monophosphate-activated protein kinase and plasma adrenaline (via protein kinase A) can be considered as essential for the exercise-induced inhibitory signals to GS.     

Signalling to glucose transport in skeletal muscle during exercise

Exercise-induced glucose uptake in skeletal muscle is mediated by an insulin-independent mechanism. Although the signalling events that increase glucose transport in response to muscle contraction are not fully elucidated, the aim of the present review is to briefly present the current understanding of the molecular signalling mechanisms involved. Glucose uptake may be regulated by Ca++-sensitive contraction-related mechanisms possibly involving protein kinase C, and by mechanisms that reflect the metabolic status of the muscle and may involve the AMP-activated protein kinase. Furthermore the p38 mitogen activated protein kinase may be involved. Still, the picture is incomplete and a substantial part of the exercise/contraction-induced signalling mechanism to glucose transport remains unknown.     

Lactate in blood,mixed skeletal muscle,and FT or ST fibres during cycle exercise in man

The relationship between muscle and blood lactate levels during progressively step-wise incrementing cycle exercise has been investigated in 10 male subjects. Steps between power outputs during exercise were 50 W and each stage, from loadless pedalling until voluntary exhaustion, lasted 4 min. Blood samples and biopsies (m. vastus lateralis) were taken for lactate determination at each power output beginning with the exercise intensity perceived by the subject as being “rather moderate”. The ratio muscle: blood lactate was greater than one at all power outputs and increased most markedly at the power output closest to that eliciting 4 mmol × I^-1 blood lactate (W_OBLA). At W_OBLA. blood lactate was positively correlated to muscle lactate concentrations which covaried widely among subjects (mean 8.3. range 4.5–14.4 mmol × kg^-l wet weight). Muscle fibres from the W_OBLA biopsy in 6 subjects were dissected out and identified as fast twitch (FT) or slow twitch (ST). No significant difference in lactate concentration was observed between pools of FT or ST fibres.     

Effect of arm-cranking on leg blood flow and noradrenaline spillover during leg exercise in man

Controversy exists whether recruitment of a large muscle mass in dynamic exercise may outstrip the pumping capacity of the heart and require neurogenic vasoconstriction in exercising muscle to prevent a fall in arterial blood pressure. To elucidate this question, seven healthy young men cycled for 70 minutes at a work load of 5540%VO_2max. At 30 to 50 minutes, arm cranking was added and total work load increased to (mean ± SE) 82 ± 4% of Vo_2max. During leg exercise, leg blood flow average 6.15 4.511 minutes^-1, mean arterial blood pressure 137 ± 4 mmHg and leg conductance 42.3 ± 2.2 ml minutes^-1 mmHg^-1. When arm cranking was added to leg cycling, leg blood flow did not change significantly, mean arterial blood pressure increased transiently to 147 ± 5 mmHg and leg vascular conductance decreased transiently to 33.5 ± 3.1 ml minutes^-1 mmHg^-1. Furthermore, arm cranking doubled leg noradrenaline spillover. When arm cranking was discontinued and leg cycling continued, leg blood flow was unchanged but mean arterial blood pressure decreased to values significantly below those measured in the first leg exercise period. Furthermore, leg vascular conductance increased transiently, and noradrenaline spillover decreased towards values measured during the first leg exercise period. It is concluded that addition of arm cranking to leg cycling increases leg noradrenaline spillover and decreases leg vascular conductance but leg blood flow remains unchanged because of a simultaneous increase in mean arterial blood pressure. The decrease in leg vascular conductance observed when arm cranking increased mean arterial blood pressure could be regarded more as a measure to prevent overperfusion than a measure to maintain arterial blood pressure.     

Excessive skeletal muscle recruitment during strenuous exercise in McArdle patients

We compared the cardiorespiratory response and muscle recruitment [as determined by electromyography (EMG)] of 37 McArdle patients [19 males, 37.4 ± 2.8 years, body mass index (BMI): 25.1 ± 4.7 kg m^?2] and 33 healthy controls (18 males, 36.4 ± 10.0 years, BMI: 25.7 ± 3.8 kg m^?2) during cycle-ergometer exercise (an incremental test to exhaustion and a 12-min submaximal constant workload test). We obtained cardiorespiratory [oxygen uptake and heart rate (HR)] and EMG data (rectus femoris and vastus lateralis muscles). During the incremental test, the patients exhibited the expected hyperkinetic cardiovascular response shown by a marked increase in the slope of the HR:Power relationship (p < 0.001). Throughout the incremental test and at the point of fatigue, the patients produced significantly less power than the controls (peak power output: 67 ± 21 vs. 214 ± 56 watts respectively, p < 0.001), yet they demonstrated significantly higher levels of muscle activity for a given absolute power. During the constant workload test, patients displayed higher levels of EMG activity than the controls during the second half of the test, despite a lower power production (34 ± 13 vs. 94 ± 29 watts respectively, p < 0.001). In conclusion, since the McArdle patients required more motor unit recruitment for a given power output, our data suggest that the state of contractility of their muscles is reduced compared with healthy people. Excessive muscle recruitment for a given load could be one of the mechanisms explaining the exercise intolerance of these patients.     

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.     

NAD in muscle of man at rest and during exercise

NAD can be used to assess the adequacy of oxygen availability to the respiratory chain. An enzymatic assay was established for NAD in human muscle biopsy samples. It gave reliable, reproducible results. The variation within and between subjects was less than 12%.Muscle NAD and lactate were determined at rest, and after bicycle ergometry work requiring 75 and (six subjects, four tests each). A positive (P<0.01) linear relationship between resting muscle NAD and percent slow twitch fibers was found, suggesting that fiber types may have different NAD content. Muscle NAD decreased during submaximal and maximal work (P<0.05). A large portion (73%) of the NAD reduction could be accounted for by increased muscle water. No relationship could be established between NAD and lactate. The negative linear relationship (P<0.01) between the muscle/blood ratio and percent slow twitch fibers is another indication of the fiber types having different metabolic responses to the activity.     

Effect of arm-cranking on leg blood flow and noradrenaline spillover during leg exercise in man.

Controversy exists whether recruitment of a large muscle mass in dynamic exercise may outstrip the pumping capacity of the heart and require neurogenic vasoconstriction in exercising muscle to prevent a fall in arterial blood pressure. To elucidate this question, seven healthy young men cycled for 70 minutes at a work load of 55-60% VO2max. At 30 to 50 minutes, arm cranking was added and total work load increased to (mean +/- SE) 82 +/- 4% of VO2max. During leg exercise, leg blood flow average 6.15 +/- .511 minutes-1, mean arterial blood pressure 137 +/- 4 mmHg and leg conductance 42.3 +/- 2.2 ml minutes-1 mmHg-1. When arm cranking was added to leg cycling, leg blood flow did not change significantly, mean arterial blood pressure increased transiently to 147 +/- 5 mmHg and leg vascular conductance decreased transiently to 33.5 +/- 3.1 ml minutes-1 mmHg-1. Furthermore, arm cranking doubled leg noradrenaline spillover. When arm cranking was discontinued and leg cycling continued, leg blood flow was unchanged but mean arterial blood pressure decreased to values significantly below those measured in the first leg exercise period. Furthermore, leg vascular conductance increased transiently, and noradrenaline spillover decreased towards values measured during the first leg exercise period. It is concluded that addition of arm cranking to leg cycling increases leg noradrenaline spillover and decreases leg vascular conductance but leg blood flow remains unchanged because of a simultaneous increase in mean arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Utilization of long-chain fatty acids in human skeletal muscle during exercise

Long-chain fatty acids (LCFA) are important sources of energy in contracting skeletal muscle: during the course of endurance exercise the contribution of LCFA in energy metabolism increases whereas when the intensity of exercise increases, the energy need is covered more and more by carbohydrates. Although this has been known for nearly 100 years, the mechanisms controlling fatty acid uptake and oxidation during various exercise modes are still not completely elucidated. Besides passive diffusion, data suggest that both membrane-associated and cytosolic fatty acid binding proteins are involved in the uptake of LCFA into skeletal muscle. However, data from human studies suggest that the regulation of fatty acid utilization in skeletal muscle during exercise lies mainly within the entrance into the mitochondria or metabolism within the mitochondria. Although possible compartmentalization within the cell makes definitive conclusions difficult, available evidence suggests that changes in malonyl CoA concentration in muscle do not play a major regulatory role in controlling LCFA oxidation during exercise in man. In contrast, it is suggested that the availability of free carnitine may play a major regulatory role in oxidation of LCFA during exercise.     

Optimal hematocrit for canine skeletal muscle during rhythmic isotonic exercise

Summary Contractile power, blood flow, O₂-uptake. and O₂-extraction during isotonic, rhythmic exercise were determined in the isolated canine gastrocnemius muscle during perfusion with blood with hematocrits between 0.21 and 0.81. The results obtained in 36 measurements on nine muscles showed that maximal O₂-delivery to the muscle is found at hematocrits between 0.5 and 0.6. Both in the range of hemodilution, and in the range of extreme hemoconcentration, O₂-delivery decreases significantly. O₂-consumption and contractile power of the muscles are almost unaffected in the hematocrit range between 0.4 and 0.7; beyond and below this hematocrit range both parameters decrease. O₂-extraction is virtually constant in the hematocrit range between 0.3 and 0.6, but increases both below and above these hematocrit levels.It is concluded that due to reduced vasodilatory reserve in working skeletal muscle compared to resting muscle the optimal hematocrit is shifted to higher values.