Luft's syndrome: O2 cost of exercise and chemical control of breathing.

The oxygen cost of exercise and chemical control of breathing were studied in a subject with Luft's syndrome, a disorder in which skeletal muscle mitochondria have a high "resting" O2 consumption which is imcreased only slightly by stimulation with excess phosphate acceptor, but a normal P/O ratio. The O2 consumption was more than three times normal (1.05 1/min) at rest but could be doubled when stimulated by maximal exercise. The O2 cost of exercise was similar to that of normal subjects. At rest, arterial blood PCO2 and ventilatory response to CO2 were normal, while ventilatory response to hypoxia was four times the predicted value. The data 1) confirm, in vivo, the normal respiratory efficiency of skeletal muscles in this disorder; 2) suggest that in vitro estimates of the extent to which mitochondrial respiration can be stimulated may not correlate with in vivo determinations; and 3) suggests that hypermetabolism per se can cause the ventilatory adjustments which are associated with exercise in normal subjects.     

Effect of voluntary exercise on H2O2 release by subsarcolemmal and intermyofibrillar mitochondria

Previous data have demonstrated that, to handle the oxidative stress encountered with training at high intensity, skeletal muscle relies on an increase in mitochondrial biogenesis, a reduced H(2)O(2) production, and an enhancement of antioxidant enzymes. In the present study, we evaluated the influence of voluntary running on mitochondrial O(2) consumption and H(2)O(2) production by intermyofibrillar mitochondria (IFM) and subsarcolemmal mitochondria (SSM) isolated from oxidative muscles in conjunction with the determination of antioxidant capacities. When mitochondria are incubated with succinate as substrate, both maximal (state 3) and resting (state 4) O(2) consumption were significantly lower in SSM than in IFM populations. Mitochondrial H(2)O(2) release per unit of O(2) consumed was 2-fold higher in SSM than in IFM. Inhibition of H(2)O(2) formation by rotenone suggests that complex I of the electron transport chain is likely the major physiological H(2)O(2)-generating system. In Lou/C rats (an inbred strain of rats of Wistar origin), neither O(2) consumption nor H(2)O(2) release by IFM and SSM were affected by long-term, voluntary wheel training. In contrast, glutathione peroxidase and catalase activity were significantly increased despite no change in oxidative capacities with long-term, voluntary exercise. Furthermore, chronic exercise enhanced heat shock protein 72 accumulation within skeletal muscle. It is concluded that the antioxidant status of muscle can be significantly improved by prolonged wheel exercise without necessitating an increase in mitochondrial oxidative capacities.     

Effects of chronic nitric oxide synthase inhibition on responses to acute exercise in swine.

Nitric oxide (NO) is potentially involved in several responses to acute exercise. We tested the hypotheses that inhibition of NO formation reduces maximal O(2) delivery to muscle, but does not affect O(2) utilization by muscle, therefore lowering maximal O(2) consumption. To test these hypotheses, swine (approximately 30 kg) drank either tap water (Con, n = 25) or water with N(G)-nitro-l-arginine methyl ester (8.0 +/- 0.4 mg x kg(-1) x day(-1) for >or=4 wk; LN, n = 24). Treatment efficacy was reflected by higher mean arterial pressure and lower plasma NO metabolite concentration in LN than Con (both P < 0.05). Swine completed two graded treadmill running tests to maximum. In the first test, O(2) consumption was determined at rest through maximal exercise intensity. O(2) consumption did not differ between groups at rest or at most exercise intensities, including maximum (Con, 40.8 +/- 1.8 ml x min(-1) x kg(-1); LN, 40.4 +/- 2.9; not significant). In the second test, tissue-specific blood flows were determined using the radiolabeled-microsphere technique. At rest, blood flows were lower (P < 0.05) in LN compared with Con for a number of tissues, including kidney, adrenal, lung, and several skeletal muscles. During both submaximal and maximal exercise, however, blood flows were similar between Con and LN for all 16 muscles examined; only blood flows to kidney (Con, 99 +/- 16 ml x min(-1) x 100 g; LN, 55 +/- 15; P < 0.05) and pancreas (Con, 25 +/- 7; LN, 6 +/- 2; P < 0.05) were lower in LN at maximum. Endothelium-dependent, but not -independent, relaxation of renal arterial segments was reduced (P < 0.05) in vitro. These data indicate that exercise-induced increases in muscle blood flows are maintained with chronic inhibition of NO formation and that maximal O(2) consumption is therefore preserved. Redundant vasodilatory pathways and/or upregulation of these pathways may underlie these findings.     

Oxygen delivery by blood determines the maximal VO2 and work rate during whole body exercise in humans: in silico studies

It has been proposed by Saltin (J Exp Biol 115: 345-354, 1985) that oxygen delivery by blood is limiting for maximal work and oxygen consumption in humans during whole body exercise but not during single-muscle exercise. To test this prediction quantitatively, we developed a static (steady-state) computer model of oxygen transport to and within human skeletal muscle during single-muscle (quadriceps) exercise and whole body (cycling) exercise. The main system fluxes, namely cardiac output and oxygen consumption by muscle, are described as a function of the "primary" parameter: work rate. The model is broadly validated by comparison of computer simulations with various experimental data. In silico studies show that, when all other parameters and system properties are kept constant, an increase in the working muscle mass from 2.5 kg (single quadriceps) to 15 kg (two legs) causes, at some critical work intensity, a drop in oxygen concentration in muscle cells to (very near) zero, and therefore oxygen supply by blood limits maximal oxygen consumption and oxidative ATP production. Therefore, the maximal oxygen consumption per muscle mass is significantly higher during single-muscle exercise than during whole body exercise. The effect is brought about by a distribution of a limited amount of oxygen transported by blood in a greater working muscle mass during whole body exercise.     

Limitations to vasodilatory capacity and .VO2 max in trained human skeletal muscle

To further explore the limitations to maximal O(2) consumption (.VO(2 max)) in exercise-trained skeletal muscle, six cyclists performed graded knee-extensor exercise to maximum work rate (WR(max)) in hypoxia (12% O(2)), hyperoxia (100% O(2)), and hyperoxia + femoral arterial infusion of adenosine (ADO) at 80% WR(max). Arterial and venous blood sampling and thermodilution blood flow measurements allowed the determination of muscle O(2) delivery and O(2) consumption. At WR(max), O(2) delivery rose progressively from hypoxia (1.0 +/- 0.04 l/min) to hyperoxia (1.20 +/- 0.09 l/min) and hyperoxia + ADO (1.33 +/- 0.05 l/min). Leg .VO(2 max) varied with O(2) availability (0.81 +/- 0.05 and 0.97 +/- 0.07 l/min in hypoxia and hyperoxia, respectively) but did not improve with ADO-mediated vasodilation (0.80 +/- 0.09 l/min in hyperoxia + ADO). Although a vasodilatory reserve in the maximally working quadriceps muscle group may have been evidenced by increased leg vascular conductance after ADO infusion beyond that observed in hyperoxia (increased blood flow but no change in blood pressure), we recognize the possibility that the ADO infusion may have provoked vasodilation in nonexercising tissue of this limb. Together, these findings imply that maximally exercising skeletal muscle may maintain some vasodilatory capacity, but the lack of improvement in leg .VO(2 max) with significantly increased O(2) delivery (hyperoxia + ADO), with a degree of uncertainty as to the site of this dilation, suggests an ADO-induced mismatch between O(2) consumption and blood flow in the exercising limb.     

Intramuscular triacylglycerol utilization in human skeletal muscle during exercise: is there a controversy?

Intramuscular triacylglyerols (IMTGs) represent a potentially important energy source for contracting human skeletal muscle. Although the majority of evidence from isotope tracer and (1)H-magnetic resonance spectroscopy (MRS) studies demonstrate IMTG utilization during exercise, controversy regarding the importance of IMTG as a metabolic substrate persists. The controversy stems from studies that measure IMTG in skeletal muscle biopsy samples and report no significant net IMTG degradation during prolonged moderate-intensity (55-70% maximal O(2) consumption) exercise lasting 90-120 min. Although postexercise decrements in IMTG levels are often reported from direct muscle measurements, the marked between-biopsy variability (approximately 23%) that has been reported with this technique in untrained subjects is larger than the expected decrease in IMTG content, effectively precluding significant findings. In contrast, recent data obtained in endurance-trained subjects demonstrated reduced variability between duplicate biopsies (approximately 12%), and significant changes in IMTG were detected after 120 min of moderate-intensity exercise. Therefore, it is our contention that the muscle biopsy, isotope tracer, and (1)H-MRS techniques report significant and energetically important oxidation of free fatty acids derived from IMTGs during prolonged moderate exercise.     

Muscle oxygen extraction and perfusion heterogeneity during continuous and intermittent static exercise.

The purpose of this study was to compare the effects of intermittent and continuous static exercise on muscle perfusion, perfusion heterogeneity, and oxygen extraction. Perfusion and oxygen uptake of quadriceps femoris muscle were measured in 10 healthy men by using positron emission tomography and [(15)O]H(2)O and [(15)O]O(2) first during intermittent static exercise [10% of maximal static force (MSF)] and thereafter during continuous static exercise at the same tension-time level (5% static; 5% of MSF). In 4 of these subjects, perfusion was measured during continuous static exercise with 10% of MSF (10% continuous) instead of the second [(15)O]O(2) measurement. Muscle oxygen consumption was similar during intermittent and 5% continuous, but muscle perfusion was significantly higher during 5% continuous. Consequently, muscle oxygen extraction fraction was lower during 5% continuous. Perfusion was also more heterogeneous during 5% continuous. When exercise intensity was doubled during continuous static exercise (from 5% continuous to 10% continuous), muscle perfusion increased markedly. These results suggest that continuous, low-intensity static exercise decreases muscle oxygen extraction and increases muscle perfusion and its heterogeneity compared with intermittent static exercise at the same relative exercise intensity.     

Progressive elevations in muscle blood flow during prolonged exercise in swine

Distribution of muscle blood flow has not been measured in man during prolonged exercise, but progressive elevations in skin flow coupled with constant cardiac output (QT) have suggested muscle blood flow may be compromised. However, previous experiments with rats demonstrated progressive increases in muscle blood flow over time during prolonged submaximal exercise. The present study was performed to study muscle blood flow in miniature swine during long-term exercise to shed light on this apparent anomaly. QT and distribution of QT were studied with radiolabeled microspheres while pigs ran on a level treadmill at a speed (10.5 km/h) requiring 71 +/- 4% of maximal O2 consumption (VO2 max). QT increased 23% from the 5th to the 30th min of exercise, whereas total skeletal muscle flow increased by 49%. Increases in flow in the muscles resulted from decreased resistance, since mean arterial pressure declined over this time period (-7%). In addition, the proportional increases in muscle flow were similar within synergistic muscle groups independent of fiber type composition (e.g., elbow extensors: 59-78%; elbow flexors: 26-40%). The factor that limited continued exercise appeared to be body temperature. Colonic temperature rose in linear fashion over time; the animals became exhausted at approximately 42 degrees C. These flow data are similar to previous findings in rats and indicate that during prolonged treadmill locomotion in quadrupedal animals muscle blood flow increases over time to near maximal levels.     

Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise: in silico studies

Skeletal muscle can maintain ATP concentration constant during the transition from rest to exercise, whereas metabolic reaction rates may increase substantially. Among the key regulatory factors of skeletal muscle energy metabolism during exercise, the dynamics of cytosolic and mitochondrial NADH and NAD+ have not been characterized. To quantify these regulatory factors, we have developed a physiologically based computational model of skeletal muscle energy metabolism. This model integrates transport and reaction fluxes in distinct capillary, cytosolic, and mitochondrial domains and investigates the roles of mitochondrial NADH/NAD+ transport (shuttling) activity and muscle glycogen concentration (stores) during moderate intensity exercise (60% maximal O2 consumption). The underlying hypothesis is that the cytosolic redox state (NADH/NAD+) is much more sensitive to a metabolic disturbance in contracting skeletal muscle than the mitochondrial redox state. This hypothesis was tested by simulating the dynamic metabolic responses of skeletal muscle to exercise while altering the transport rate of reducing equivalents (NADH and NAD+) between cytosol and mitochondria and muscle glycogen stores. Simulations with optimal parameter estimates showed good agreement with the available experimental data from muscle biopsies in human subjects. Compared with these simulations, a 20% increase (or approximately 20% decrease) in mitochondrial NADH/NAD+ shuttling activity led to an approximately 70% decrease (or approximately 3-fold increase) in cytosolic redox state and an approximately 35% decrease (or approximately 25% increase) in muscle lactate level. Doubling (or halving) muscle glycogen concentration resulted in an approximately 50% increase (or approximately 35% decrease) in cytosolic redox state and an approximately 30% increase (or approximately 25% decrease) in muscle lactate concentration. In both cases, changes in mitochondrial redox state were minimal. In conclusion, the model simulations of exercise response are consistent with the hypothesis that mitochondrial NADH/NAD+ shuttling activity and muscle glycogen stores affect primarily the cytosolic redox state. Furthermore, muscle lactate production is regulated primarily by the cytosolic redox state.     

Integrative control of the skeletal muscle microcirculation in the maintenance of arterial pressure during exercise.

Skeletal muscle blood flow and vascular conductance are influenced by numerous factors that can be divided into two general categories: central cardiovascular control mechanisms and local vascular control mechanisms. Central cardiovascular control mechanisms are thought to be designed primarily for the maintenance of arterial pressure and central cardiovascular homeostasis, whereas local vascular control mechanisms are thought to be designed primarily for the maintenance of muscle homeostasis. To support the high metabolic rates that can be generated during muscle contraction, skeletal muscle has a tremendous capacity to vasodilate and increase oxygen and nutrient delivery. During whole body dynamic exercise at maximal oxygen consumption (VO2 max), the skeletal muscle receives 85-90% of cardiac output. Yet despite receiving such a large fraction of cardiac output during high-intensity exercise, a vasodilator reserve remains with the potential to produce further elevations in skeletal muscle vascular conductance and blood flow. However, because maximal cardiac output is reached during exercise at VO2 max, further elevations in muscle vascular conductance would produce a fall in arterial pressure. Therefore, limits on muscle perfusion must be imposed during whole body exercise to prevent such drops in pressure. Effective arterial pressure control in response to a potentially hypotensive challenge during high-intensity exercise occurs primarily through reflex-mediated increases in sympathetic nerve activity, which are capable of modulating vasomotor tone of the skeletal muscle resistance vasculature. Thus skeletal muscle vascular conductance and perfusion are primarily mediated by local factors at rest and during exercise, but other centrally mediated control systems are superimposed on the dominant local control mechanisms to provide an integrated regulation of both arterial pressure and skeletal muscle vascular conductance and perfusion during whole body dynamic exercise.     

Impaired cardiac reserve and severely diminished skeletal muscle O₂ utilization mediate exercise intolerance in Barth syndrome

Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of skeletal muscle O(2) extraction/utilization and 2) exercise intolerance in BTHS is related to impaired O(2) extraction/utilization, impaired cardiac function, or both. Participants with BTHS (age: 17 ± 5 yr, n = 15) and control participants (age: 13 ± 4 yr, n = 9) underwent graded exercise testing on a cycle ergometer with continuous ECG and metabolic measurements. Echocardiography was performed at rest and at peak exercise. Near-infrared spectroscopy of the vastus lateralis muscle was continuously recorded for measurements of skeletal muscle O(2) extraction. Adjusting for age, peak O(2) consumption (16.5 ± 4.0 vs. 39.5 ± 12.3 ml·kg(-1)·min(-1), P < 0.001) and peak work rate (58 ± 19 vs. 166 ± 60 W, P < 0.001) were significantly lower in BTHS than control participants. The percent increase from rest to peak exercise in ejection fraction (BTHS: 3 ± 10 vs. control: 19 ± 4%, P < 0.01) was blunted in BTHS compared with control participants. The muscle tissue O(2) saturation change from rest to peak exercise was paradoxically opposite (BTHS: 8 ± 16 vs. control: -5 ± 9, P < 0.01), and the deoxyhemoglobin change was blunted (BTHS: 0 ± 12 vs. control: 10 ± 8, P < 0.09) in BTHS compared with control participants, indicating impaired skeletal muscle extraction in BTHS. In conclusion, severe exercise intolerance in BTHS is due to both cardiac and skeletal muscle impairments that are consistent with cardiac and skeletal mitochondrial myopathy. These findings provide further insight to the pathophysiology of BTHS.     

Interaction of factors determining oxygen uptake at the onset of exercise.

Considerable debate surrounds the issue of whether the rate of adaptation of skeletal muscle O2 consumption (QO2) at the onset of exercise is limited by 1) the inertia of intrinsic cellular metabolic signals and enzyme activation or 2) the availability of O2 to the mitochondria, as determined by an extrinsic inertia of convective and diffusive O2 transport mechanisms. This review critically examines evidence for both hypotheses and clarifies important limitations in the experimental and theoretical approaches to this issue. A review of biochemical evidence suggests that a given respiratory rate is a function of the net drive of phosphorylation potential and redox potential and cellular mitochondrial PO2 (PmitoO2). Changes in both phosphorylation and redox potential are determined by intrinsic metabolic inertia. PmitoO2 is determined by the extrinsic inertia of both convective and diffusive O2 transport mechanisms during the adaptation to exercise and the rate of mitochondrial O2 utilization. In a number of exercise conditions, PmitoO2 appears to be within a range capable of modulating muscle metabolism. Within this context, adjustments in the phosphate energy state of the cell would serve as a cytosolic "transducer," linking ATP consumption with mitochondrial ATP production and, therefore, O2 consumption. The availability of reducing equivalents and O2 would modulate the rate of adaptation of QO2.     

Training effects on regional blood flow response to maximal exercise in foxhounds

The effect of training on the regional blood flow response to maximal exercise was investigated in the foxhound. Training consisted of 8-12 wk of treadmill running at 80% of maximal heart rate 1 h/day for 5 days/wk and resulted in a 31% increase in maximal O2 consumption, a 28% increase in maximal cardiac output, and a 23% decrease in systemic vascular resistance during maximal exercise. Blood flow to the heart, diaphragm, brain, skin, and 9 of 10 muscles investigated was similar during maximal exercise pre- and posttraining; however, blood flow to the gastrocnemius muscle was greater posttraining than it was pretraining. Blood flow to the stomach, small intestine, and pancreas decreased during maximal exercise pre- and posttraining; however, blood flow to the large intestine, spleen, liver, adrenal glands, and kidneys decreased during maximal exercise only posttraining. In addition, a larger decrease in blood flow to the stomach during maximal exercise was found posttraining compared with pretraining. These results demonstrate that blood flow to skeletal muscle, the kidneys, and the splanchnic region of the foxhound during maximal exercise can be significantly altered by dynamic exercise training.     

Muscle oxygen transport and utilization in heart failure: implications for exercise (in)tolerance

The defining characteristic of chronic heart failure (CHF) is an exercise intolerance that is inextricably linked to structural and functional aberrations in the O(2) transport pathway. CHF reduces muscle O(2) supply while simultaneously increasing O(2) demands. CHF severity varies from moderate to severe and is assessed commonly in terms of the maximum O(2) uptake, which relates closely to patient morbidity and mortality in CHF and forms the basis for Weber and colleagues' (167) classifications of heart failure, speed of the O(2) uptake kinetics following exercise onset and during recovery, and the capacity to perform submaximal exercise. As the heart fails, cardiovascular regulation shifts from controlling cardiac output as a means for supplying the oxidative energetic needs of exercising skeletal muscle and other organs to preventing catastrophic swings in blood pressure. This shift is mediated by a complex array of events that include altered reflex and humoral control of the circulation, required to prevent the skeletal muscle "sleeping giant" from outstripping the pathologically limited cardiac output and secondarily impacts lung (and respiratory muscle), vascular, and locomotory muscle function. Recently, interest has also focused on the dysregulation of inflammatory mediators including tumor necrosis factor-α and interleukin-1β as well as reactive oxygen species as mediators of systemic and muscle dysfunction. This brief review focuses on skeletal muscle to address the mechanistic bases for the reduced maximum O(2) uptake, slowed O(2) uptake kinetics, and exercise intolerance in CHF. Experimental evidence in humans and animal models of CHF unveils the microvascular cause(s) and consequences of the O(2) supply (decreased)/O(2) demand (increased) imbalance emblematic of CHF. Therapeutic strategies to improve muscle microvascular and oxidative function (e.g., exercise training and anti-inflammatory, antioxidant strategies, in particular) and hence patient exercise tolerance and quality of life are presented within their appropriate context of the O(2) transport pathway.     

Estimation of capillary density in human skeletal muscle based on maximal oxygen consumption rates

A previously developed Krogh-type theoretical model was used to estimate capillary density in human skeletal muscle based on published measurements of oxygen consumption, arterial partial pressure of oxygen, and blood flow during maximal exercise. The model assumes that oxygen consumption in maximal exercise is limited by the ability of capillaries to deliver oxygen to tissue and is therefore strongly dependent on capillary density, defined as the number of capillaries per unit cross-sectional area of muscle. Based on an analysis of oxygen transport processes occurring at the microvascular level, the model allows estimation of the minimum number of straight, evenly spaced capillaries required to achieve a given oxygen consumption rate. Estimated capillary density values were determined from measurements of maximal oxygen consumption during knee extensor exercise and during whole body cycling, and they range from 459 to 1,468 capillaries/mm2. Measured capillary densities, obtained with either histochemical staining techniques or electron microscopy on quadriceps muscle biopsies from healthy subjects, are generally lower, ranging from 123 to 515 capillaries/mm2. This discrepancy is partly accounted for by the fact that capillary density decreases with muscle contraction and muscle biopsy samples typically are strongly contracted. The results imply that estimates of maximal oxygen transport rates based on capillary density values obtained from biopsy samples do not fully reflect the oxygen transport capacity of the capillaries in skeletal muscle.     

Skeletal muscle intracellular PO(2) assessed by myoglobin desaturation: response to graded exercise.

The relationship between skeletal muscle intracellular PO(2) (iPO(2)) and progressive muscular work has important implications for the understanding of O(2) transport and utilization. Presently there is debate as to whether iPO(2) falls progressively with increasing O(2) demand or reaches a plateau from moderate to maximal metabolic demand. Thus, using (1)H magnetic resonance spectroscopy of myoglobin (Mb), we studied cellular oxygenation during progressive single-leg knee extensor exercise from unweighted to 100% of maximal work rate in six active human subjects. In all subjects, the Mb peak at 73 ppm was not visible at rest, whereas the peak was small or indistinguishable from the noise in the majority of subjects during progressive exercise from unweighted to 50-60% of maximum work rate. In contrast, beyond this exercise intensity, a Mb peak of consistent magnitude was discernible in all subjects. When a Mb half saturation of 3.2 Torr was used, the calculated skeletal muscle PO(2) was variable before 60% of maximum work rate but in general was relatively high (>18 Torr, the measurable PO(2) with the poorest signal-to-noise ratio, in the majority of cases), whereas beyond this exercise intensity iPO(2) fell to a relatively uniform and invariant level of 3.8 +/- 0.5 Torr across all subjects. These results do not support the concept of a progressive linear fall in iPO(2) across increasing work rates. Instead, this study documents variable but relatively high iPO(2) from rest to moderate exercise and again confirms that from 50-60% of maximum work rate iPO(2) reaches a plateau that is then invariant with increasing work rate.     

Hypohydration does not impair skeletal muscle glycogen resynthesis after exercise

The purpose of this investigation was to examine the effects of moderate hypohydration (HY) on skeletal muscle glycogen resynthesis after exhaustive exercise. On two occasions, eight males completed 2 h of intermittent cycle ergometer exercise (4 bouts of 17 min at 60% and 3 min at 80% of maximal O2 consumption/10 min rest) to reduce muscle glycogen concentrations (control values 711 +/- 41 mumol/g dry wt). During one trial, cycle exercise was followed by several hours of light upper body exercise in the heat without fluid replacement to induce HY (-5% body wt); in the second trial, sufficient water was ingested during the upper body exercise and heat exposure to maintain euhydration (EU). In both trials, 400 g of carbohydrate were ingested at the completion of exercise and followed by 15 h of rest while the desired hydration level was maintained. Muscle biopsy samples were obtained from the vastus lateralis immediately after intermittent cycle exercise (T1) and after 15 h of rest (T2). During the HY trial, the muscle water content was lower (P less than 0.05) at T1 and T2 (288 +/- 9 and 265 +/- 5 ml/100 g dry wt, respectively; NS) than during EU (313 +/- 8 and 301 +/- 4 ml/100 g dry wt, respectively; NS). Muscle glycogen concentration was not significantly different during EU and HY at T1 (200 +/- 35 vs. 251 +/- 50 mumol/g dry wt) or T2 (452 +/- 34 vs. 491 +/- 35 mumol/g dry wt). These data indicate that, despite reduced water content during the first 15 h after heavy exercise, skeletal muscle glycogen resynthesis is not impaired.     

Single-leg cycle training is superior to double-leg cycling in improving the oxidative potential and metabolic profile of trained skeletal muscle

Single-leg cycling may enhance the peripheral adaptations of skeletal muscle to a greater extent than double-leg cycling. The purpose of the current study was to determine the influence of 3 wk of high-intensity single- and double-leg cycle training on markers of oxidative potential and muscle metabolism and exercise performance. In a crossover design, nine trained cyclists (78 ± 7 kg body wt, 59 ± 5 ml·kg(-1)·min(-1) maximal O(2) consumption) performed an incremental cycling test and a 16-km cycling time trial before and after 3 wk of double-leg and counterweighted single-leg cycle training (2 training sessions per week). Training involved three (double) or six (single) maximal 4-min intervals with 6 min of recovery. Mean power output during the single-leg intervals was more than half that during the double-leg intervals (198 ± 29 vs. 344 ± 38 W, P < 0.05). Skeletal muscle biopsy samples from the vastus lateralis revealed a training-induced increase in Thr(172)-phosphorylated 5'-AMP-activated protein kinase α-subunit for both groups (P < 0.05). However, the increase in cytochrome c oxidase subunits II and IV and GLUT-4 protein concentration was greater following single- than double-leg cycling (P < 0.05). Training-induced improvements in maximal O(2) consumption (3.9 ± 6.2% vs. 0.6 ± 3.6%) and time-trial performance (1.3 ± 0.5% vs. 2.3 ± 4.2%) were similar following both interventions. We conclude that short-term high-intensity single-leg cycle training can elicit greater enhancement in the metabolic and oxidative potential of skeletal muscle than traditional double-leg cycling. Single-leg cycling may therefore provide a valuable training stimulus for trained and clinical populations.     

Effects of ATP-induced leg vasodilation on VO2 peak and leg O2 extraction during maximal exercise in humans

During maximal whole body exercise VO2 peak is limited by O2 delivery. In turn, it is though that blood flow at near-maximal exercise must be restrained by the sympathetic nervous system to maintain mean arterial pressure. To determine whether enhancing vasodilation across the leg results in higher O2 delivery and leg VO2 during near-maximal and maximal exercise in humans, seven men performed two maximal incremental exercise tests on the cycle ergometer. In random order, one test was performed with and one without (control exercise) infusion of ATP (8 mg in 1 ml of isotonic saline solution) into the right femoral artery at a rate of 80 microg.kg body mass-1.min-1. During near-maximal exercise (92% of VO2 peak), the infusion of ATP increased leg vascular conductance (+43%, P<0.05), leg blood flow (+20%, 1.7 l/min, P<0.05), and leg O2 delivery (+20%, 0.3 l/min, P<0.05). No effects were observed on leg or systemic VO2. Leg O2 fractional extraction was decreased from 85+/-3 (control) to 78+/-4% (ATP) in the infused leg (P<0.05), while it remained unchanged in the left leg (84+/-2 and 83+/-2%; control and ATP; n=3). ATP infusion at maximal exercise increased leg vascular conductance by 17% (P<0.05), while leg blood flow tended to be elevated by 0.8 l/min (P=0.08). However, neither systemic nor leg peak VO2 values where enhanced due to a reduction of O2 extraction from 84+/-4 to 76+/-4%, in the control and ATP conditions, respectively (P<0.05). In summary, the VO2 of the skeletal muscles of the lower extremities is not enhanced by limb vasodilation at near-maximal or maximal exercise in humans. The fact that ATP infusion resulted in a reduction of O2 extraction across the exercising leg suggests a vasodilating effect of ATP on less-active muscle fibers and other noncontracting tissues and that under normal conditions these regions are under high vasoconstrictor influence to ensure the most efficient flow distribution of the available cardiac output to the most active muscle fibers of the exercising limb.     

Muscle glycogen depletion and subsequent replenishment affect anaerobic capacity of horses.

The purpose of this study was to determine the effect of muscle glycogen depletion and subsequent replenishment on anaerobic capacity of horses. In a blinded crossover study, seven fit horses performed glycogen-depleting exercise on two occasions. Horses were infused after glycogen-depleting exercise with either 6 g/kg body wt of glucose as a 13.5% solution in 0.9% NaCl (Glu) or with 0.9% NaCl (Sal) of equivalent volume. Subsequently, horses performed a high-speed exercise test (120% of maximal rate of oxygen consumption) to estimate maximum accumulated oxygen deficit. Replenishment of muscle glycogen was greater (P < 0.05) in Glu [from 24.7 +/- 7.2 (SE) to 116.5 +/- 7 mmol/kg wet wt before and after infusion, respectively] than in Sal (from 23.4 +/- 7.2 to 47.8 +/- 5.7 mmol/kg wet wt before and after infusion, respectively). Run time to fatigue during the high-speed exercise test (97.3 +/- 8.2 and 70.8 +/- 8.3 s, P < 0.05), maximal accumulated oxygen deficit (105.7 +/- 9.3 and 82.4 +/- 10.3 ml O(2) equivalent/kg, P < 0.05), and blood lactate concentration at the end of the high-speed exercise test (11.1 +/- 1.4 and 9.2 +/- 3.7 mmol/l, P < 0.05) were greater for Glu than for Sal, respectively. We concluded that decreased availability of skeletal muscle glycogen stores diminishes anaerobic power generation and capacity for high-intensity exercise in horses.