Exercise In Human Subjects Research Articles

Monitoring of Lactate in Interstitial Fluid, Saliva and Sweat by Electrochemical Biosensor: The Uncertainties of Biological Interpretation

Lactate electrochemical biosensors were fabricated using Pediococcus sp lactate oxidase (E.C. 1.1.3.2), an external polyurethane membrane laminate diffusion barrier and an internal ionomeric polymer barrier (sulphonated polyether ether sulphone polyether sulphone, SPEES PES). In a needle embodiment, a Pt wire working electrode was retained within stainless steel tubing serving as pseudoreference. The construct gave linearity to at least 25 mM lactate with 0.17 nA/mM lactate sensitivity. A low permeability inner membrane was also unexpectedly able to increase linearity. Responses were oxygen dependent at pO2 < 70 mmHg, irrespective of the inclusion of an external diffusion barrier membrane. Subcutaneous tissue was monitored in Sprague Dawley rats, and saliva and sweat during exercise in human subjects. The tissue sensors registered no response to intravenous Na lactate, indicating a blood-tissue lactate barrier. Salivary lactate allowed tracking of blood lactate during exercise, but lactate levels were substantially lower than those in blood (0–3.5 mM vs. 1.6–12.1 mM), with variable degrees of lactate partitioning from blood, evident both between subjects and at different exercise time points. Sweat lactate during exercise measured up to 23 mM but showed highly inconsistent change as exercise progressed. We conclude that neither tissue interstitial fluid nor sweat are usable as surrogates for blood lactate, and that major reappraisal of lactate sensor use is indicated for any extravascular monitoring strategy for lactate.

CD4+ T cell activation and associated susceptibility to HIV-1 infection in vitro increased following acute resistance exercise in human subjects.

Early studies in exercise immunology suggested acute bouts of exercise had an immunosuppressive effect in human subjects. However, recent data, show acute bouts of combined aerobic and resistance training increase both lymphocyte activation and proliferation. We quantified resistance exercise‐induced changes in the activation state of CD4+ T lymphocytes via surface protein expression and using a medically relevant model of infection (HIV‐1). Using a randomized cross‐over design, 10 untrained subjects completed a control and exercise session. The control session consisted of 30‐min seated rest while the exercise session entailed 3 sets × 10 repetitions of back squat, leg press, and leg extensions at 70% 1‐RM with 2‐min rest between each set. Venous blood samples were obtained pre/post each session. CD4+ T lymphocytes were isolated from whole blood by negative selection. Expression of activation markers (CD69 & CD25) in both nonstimulated and stimulated (costimulation through CD3+CD28) cells were assessed by flow cytometry. Resistance exercised‐induced effects on intracellular activation was further evaluated via in vitro infection with HIV‐1. Nonstimulated CD4+ T lymphocytes obtained postexercise exhibited elevated CD25 expression following 24 h in culture. Enhanced HIV‐1 replication was observed in cells obtained postexercise. Our results demonstrate that an acute bout of resistance exercise increases the activation state of CD4+ T lymphocytes and results in a greater susceptibility to HIV‐1 infection in vitro. These findings offer further evidence that exercise induces activation of T lymphocytes and provides a foundation for the use of medically relevant pathogens as indirect measures of intracellular activation.

T cell activation and proliferation following acute exercise in human subjects is altered by storage conditions and mitogen selection

Recent work investigating exercise induced changes in immunocompetence suggests that some of the ambiguity in the literature is resultant from different cell isolation protocols and mitogen selection. To understand this effect, we compared post-exercise measures of T cell activation and proliferation using two different stimulation methods (costimulation through CD28 or stimulation with phytohaemagglutinin [PHA]). Further, we investigated whether exercise induced changes are maintained when T cell isolation from whole blood is delayed overnight in either a room temperature or chilled (4°C) environment. As expected, an increased proliferation response was observed post-exercise in T cells isolated from whole blood of previously trained individuals immediately after blood collection. Also, cells stimulated with PHA after resting overnight in whole blood were not adversely impacted by the storage conditions. In contrast, allowing cells to rest overnight in whole blood prior to stimulation through CD28, lessened the proliferation observed by cells following exercise rendering both the room temperature and chilled samples closer to the results seen in the control condition. Changes in early markers of activation (CD25), followed a similar pattern, with activation in PHA stimulated cells remaining fairly robust after overnight storage; whereas cell activation following stimulation through CD3+CD28 was disproportionately decreased by the influence of overnight storage. These findings indicate that decisions regarding cell stimulation methods need to be paired with the timeline for T cell isolation from whole blood. These considerations will be especially important for field based studies of immunocompetence where there is a delay in getting whole blood samples to a lab for processing as well as clinical applications where a failure to isolate T cells in a timely manner may result in loss of the response of interest.

The Relationship Between Activity Pattern and Muscle Adaptation in Skeletal Muscle

Muscle is highly plastic in terms of size (maximum force), speed, maximum power, and endurance. Well-controlled studies in animals have shown that the adult skeletal muscle fiber has a remarkable ability to modify its gene expression so that with long-term substantial changes in the daily activity pattern the contractile phenotype can be modified across the whole spectrum of fiber type found in control muscle. The contractile phenotype in this context includes the isoform content of myosin and therefore the maximum velocity of shortening, the mitochondrial content and therefore the specific force and aerobic capacity (endurance), and the calcium handling proteins and therefore the speed of activation and relaxation. With voluntary exercise in human subjects, similar responses are observed, although the degree of transformation is restricted by the practical limitations of exercise dosing to changes in mitochondrial activity and muscle size rather than the more profound changes in contractile protein isoform that can be induced with artificial activation over a substantial proportion of the day.

ACTN3genotype and modulation of skeletal muscle response to exercise in human subjects

α-Actinin-3 is a Z-disc protein expressed only in type II muscle fibers. A polymorphism in the ACTN3 gene (R577X) results in lack of α-actinin-3 in XX genotype. The prevalence of the mutated X-allele is lower among power/sprint oriented athletes compared with controls, indicating that the lack of α-actinin-3 is detrimental in these sports, but a mechanistic link has not been established. Results from Actn3-knockout (KO) mouse model suggest that α-actinin-3 may affect muscle mass and muscle glycogen levels. In the present investigation we examined muscle fiber type composition, cross-sectional fiber area (CSA), and muscle glycogen levels at baseline in 143 human subjects with different ACTN3 genotypes. In addition, hypertrophy signaling and glycogen utilization in response to sprint exercise were studied in a subset of subjects. Glycogen utilization was analyzed in separate pools of type I and type II fibers. No differences in fiber type composition, CSA, or muscle glycogen levels were observed at baseline across the ACTN3 genotypes. However, the sprint exercise-induced increase in phosphorylation of mTOR and p70S6k was smaller in XX than in RR+RX (P = 0.03 and P = 0.01, respectively), indicating a less pronounced activation of hypertrophy signaling in XX. Glycogen utilization during sprint exercise varied across ACTN3 genotypes in type II fibers (P = 0.03) but not in type I fibers (P = 0.38). The present results are in accordance with findings from the KO mice and reinforce the hypothesis that ACTN3 genotype-associated differences in muscle mass and glycogen utilization provide a mechanistic explanation for the modulation of human performance by the ACTN3 genotype.

Voluntary exercise regionally augments rates of cerebral protein synthesis

Exercise is a natural form of neurophysiologic stimulation that has known benefits for mental health, maintenance of cerebral function, and stress reduction. Exercise is known to induce an upregulation of brain-derived neurotrophic factor and this is thought to be involved in associated increases in neural plasticity. Protein synthesis is also an essential component of adaptive plasticity. We hypothesized that exercise may stimulate changes in brain protein synthesis as part of its effects on plasticity. Here, we applied the quantitative autoradiographic L-[1-14C]leucine method to the in vivo determination of regional rates of cerebral protein synthesis (rCPS) in adult rats following a seven day period of voluntary wheel-running and their sedentary counterparts. In four of 21 brain regions examined, the mean values of rCPS in the exercised rats were statistically significantly higher than in sedentary controls; regions affected were paraventricular hypothalamic nucleus, ventral hippocampus as a whole, CA1 pyramidal cell layer in ventral hippocampus, and frontal cortex. Increases in rCPS approached statistical significance in dentate gyrus of the ventral hippocampus. Our results affirm the value of exercise in encouraging hippocampal and possibly cortical neuroplasticity, and also suggest that exercise may modulate stimulation of stress-response pathways. Ultimately, our study indicates that measurement of rCPS with PET might be used as a marker of brain response to exercise in human subjects.

S‐Glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast‐twitch muscle fibres of rats and humans

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10 [Ca2+] at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mM) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnI(f)) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnI(f) were blocked by N-ethylmaleimide (NEM). S-nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnI(f). In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnI(f). When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnI(f), DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S-glutathionylation of TnI(f) (latter examined only in toad). Following 40 min of cycling exercise in human subjects (at ∼60% peak oxygen consumption), TnI(f) in vastus lateralis muscle displayed a marked increase in S-glutathionylation (∼4-fold). These findings show that S-glutathionylation of TnI(f), most probably at Cys133, increases the Ca2+ sensitivity of the contractile apparatus, and that this occurs in exercising humans, with likely beneficial effects on performance.

Enhanced rates of muscle protein synthesis and elevated mTOR signalling following endurance exercise in human subjects

The major aim of this study was to determine the fractional rate of protein synthesis (FSR) during the early period of recovery after intensive aerobic exercise in the absence of nutritional supplementation. Sixteen male subjects performed one-legged cycling exercise for 1 h at approx. 65-70% of their one-legged maximal oxygen uptake. Using the stable isotope technique, the FSR in the vastus lateralis of both legs were determined during two periods, 0-90 min (n = 8) and 90-180 min (n = 8) after exercise. Biopsies were taken from both exercising and resting muscle before exercise, immediately after and following 90 or 180 min of recovery. During the initial 90 min of recovery, FSR in the exercising muscle tended to be higher than in the resting muscle (1.57 ± 0.12 vs. 1.44 ± 0.07% 24 h(-1); P = 0.1) and was significantly higher during the period 90-180 min after exercise (1.74 ± 0.14 vs. 1.43 ± 0.12% 24 h(-1) ; P < 0.05). Exercise induced a 60% increase (P < 0.05) in phosphorylation of mTOR and a fivefold increase (P < 0.05) in Thr(389) phosphorylation of p70S6 kinase as well as a 30% reduction (P < 0.05) in phosphorylation of eEF2. Phosphorylation of AMP-activated protein kinase was enhanced by 40% (P < 0.05) after exercise, but no significant effect on phosphorylation of Akt, or eIF2Bε was observed immediately after exercise. These findings indicate that during the first 3 h of recovery after intensive endurance exercise FSR gradually increases. Moreover, a stimulation of the mTOR-signalling pathway may be at least partially responsible for this elevated protein synthesis.

Physical Exercise and Cognitive Recovery in Acquired Brain Injury: A Review of the Literature

Physical exercise has been shown to play an ever-broadening role in the maintenance of overall health and has been implicated in the preservation of cognitive function in both healthy elderly and demented populations. Animal and human studies of acquired brain injury (ABI) from trauma or vascular causes also suggest a possible role for physical exercise in enhancing cognitive recovery. A review of the literature was conducted to explore the current understanding of how physical exercise impacts the molecular, functional, and neuroanatomic status of both intact and brain-injured animals and humans. Searches of the MEDLINE, CINHAL, and PsychInfo databases yielded an extensive collection of animal studies of physical exercise in ABI. Animal studies strongly tie physical exercise to the upregulation of multiple neural growth factor pathways in brain-injured animals, resulting in both hippocampal neurogenesis and functional improvements in memory. A search of the same databases for publications involving physical exercise in human subjects with ABI yielded 24 prospective and retrospective studies. Four of these evaluated cognitive outcomes in persons with ABI who were involved in physical exercise. Three studies cited a positive association between exercise and improvements in cognitive function, whereas one observed no effect. Human exercise interventions varied greatly in duration, intensity, and level of subject supervision, and tools for assessing neurocognitive changes were inconsistent. There is strong evidence in animal ABI models that physical exercise facilitates neurocognitive recovery. Physical exercise interventions are safe in the subacute and rehabilitative phases of recovery for humans with ABI. In light of strong evidence of positive effects in animal studies, more controlled, prospective human interventions are warranted to better explore the neurocognitive effects of physical exercise on persons with ABI.

Effects of exercise‐induced weight loss on acylated and unacylated ghrelin in overweight children

Controversial data on ghrelin concentration during exercise in human subjects have been published. We tested the hypothesis that exercise could affect acylated ghrelin (AG) and unacylated ghrelin (UAG), which could partly explain the previously reported inconsistent findings on the association of exercise with changes in ghrelin. A prospective randomized study. We randomized 17 overweight volunteers (11-year-old boys) to a 12-week combined exercise group (EG, n = 8) or control group (CG, n = 9). At baseline, 1, 4 and 12 weeks, we measured body weight and composition, insulin, leptin, total ghrelin and acylated ghrelin. Compared with the CG, body weight, percentage body fat and homeostatic model assessment (HOMA) indices were significantly lower throughout the 12 weeks in the EG. Total ghrelin and UAG levels gradually increased to 131.9 +/- 5.2% and 130.4 +/- 5.2% of baseline, respectively, at week 12 in the EG, whereas AG concentration remained unchanged throughout the 12 weeks both within each group and between the groups. At week 12, there were differences in the total ghrelin level and UAG level between the groups. This study shows an increase in unacylated acylated ghrelin and unchanged acylated ghrelin after a 12-week combined exercise programme in overweight children. These findings provide evidence of favourable effects of exercise on improving energy metabolism.

Bimodal Recovery Pattern in Human Skeletal Muscle Induced by Exhaustive Stretch-Shortening Cycle Exercise

Recovery of force and stretch reflex from exhaustive stretch-shortening cycle (SSC) exercise is usually bimodal, characterized as immediate exercise-induced performance reduction, with its quick recovery followed by a longer-lasting reduction in performance. A clear parallel exists between the respective changes in performance, neural activation, and metabolic or structural exercise-induced changes. This implies the existence of potential coupling between muscle failure and the induced neural adjustments that take place along its recovery. The present study was designed to explore the evidence of this coupling more thoroughly. H- and stretch reflexes were measured before and periodically after exhaustive SSC exercise in human subjects. Several markers of muscle damage and inflammation were also measured during the 8-d postexercise follow-up period. The results indicate that acute changes of H- and stretch reflex patterns and maximal isometric force are associated with significant increases in lactate, interleukin 6, and prostaglandin E2 concentrations. The delayed changes in reflexes and isometric force occurred concomitantly with increases in muscle thickness, C reactive protein, and substance P concentrations and also in serum creatine kinase activity. The immediate postexercise decreases in H- and stretch reflexes are probably partially caused by activation of group III and IV afferent fibers by high lactate concentration in combination with possible increases in potassium outflow. Both of these parameters recovered quickly (i.e., 2 h after exercise). The events after the 2-h postexercise point are very likely to be related to muscle damage and associated inflammation. Group III and IV afferent fibers are probably reactivated during this period by mechanical factors.

Effect of carbohydrate ingestion on brain exchange of amino acids during sustained exercise in human subjects

This study investigated the effect of prolonged exercise with and without carbohydrate intake on the brain exchange of amino acids, especially focussing on tryptophan and branched-chain amino acids (BCAA). Five male subjects exercised for 3 h on a cycle ergometer at 200 +/- 7 W on two occasions; either supplemented with a 6% carbohydrate solution or with flavoured water (placebo). Catheters were inserted into the right internal jugular vein and the radial artery of the non-dominant arm. The brain exchange of amino acids during exercise was calculated from the arterial-jugular venous concentration difference multiplied by plasma flow. About 106 micromol (22 mg) of tryptophan was taken up by the brain during exercise in the placebo trial, whereas no significant uptake was observed in the carbohydrate trial. In accordance, the arterial concentration of free tryptophan increased from 12 +/- 1 to 20 +/- 2 micromol L(-1) during the placebo trial and was significantly higher compared with the glucose trial (14 +/- 1 micromol L(-1) at the end of exercise). Also, the arterial concentration of total tryptophan (free and albumin-bound) increased during the first 30 min of exercise in both trials, but returned to the basal level at 180 min of exercise. In both trials, BCAA were taken up by the brain while glutamine was released. The present data show that both tryptophan and BCAA are taken up by the brain during prolonged exercise, and we suggest that the cerebral uptake of tryptophan may relate to increased synthesis of serotonin (5-HT) in the brain.

Physiological factors that regulate the use of endogenous fat and carbohydrate fuels during endurance exercise

Exercise causes a dramatic increase in energy requirements because of the metabolic needs of working muscles. Exercise-dependent factors regulate fuel use. Absolute exercise intensity determines the exercise-induced increase in energy demands, whereas exercise intensity relative to an individual's maximal aerobic capacity (VO2max) determines the proportional contribution of different fuel sources (i.e. plasma glucose, plasma fatty acids, muscle glycogen and intramuscular triacylglycerols). Endurance training increases aerobic capacity in muscle and the oxidation of fat during exercise. In addition, exercise-independent factors, such as diet composition, sex, age, and body composition also influence substrate use during exercise. The present review discusses the regulation of substrate use during exercise in human subjects, with a focus on the role of exercise-independent factors.

Effect of simple motor performance on regional dopamine release in the striatum in Parkinson disease patients and healthy subjects: a positron emission tomography study.

To investigate changes in dopamine release in the striatum during motor exercise in human subjects with and without striatal dopamine denervation, eight healthy subjects and eight patients with Parkinson disease (PD) were measured during unilateral foot extension/flexion movement using positron emission tomography with [11C]raclopride. Five subjects in each group were later scanned in the resting condition. Estimation of binding potential (k3/k4) of [11C]raclopride was based on Logan plot method. Significant reductions in [11C]raclopride k3/k4 were found in the dorsal putamen contralateral to the exercise side in the healthy group and ipsilaterally in the PD group. Spearman rank correlation analysis showed that [11C]raclopride k3/k4 correlated inversely with the decrease in performance (velocity and motion range) in the dorsal putamen contralaterally in the healthy group and ipsilaterally in the PD group. These results suggest that simple but laborious motor exercise (motor stimulation) generates significant dopamine release in the dorsal striatum contralateral to the motor execution in humans. Lack of the crossed pattern and ipsilateral increase in dopamine release in the dorsal striatum during the unilateral limb movement may reflect the pathophysiology for hypokinetic and insufficient coordinating movement in PD.

Exercise and skeletal muscle gene expression.

1. Skeletal muscle is a complex and heterogenous tissue capable of remarkable adaptation in response to exercise training. The role of gene transcription, as an initial target to control protein synthesis, is poorly understood. 2. Mature myofibres contain several hundred nuclei, all of which maintain transcriptional competency, although the localized responsiveness of nuclei is not well known. Myofibres are capable of hypertrophy. These processes require the activation and myogenic differentiation of mononuclear satellite cells that fuse with the enlarging or repairing myofibre. 3. A single bout of exercise in human subjects is capable of activating the expression of many diverse groups of genes. 4. The impact of repeated exercise bouts, typical of exercise training, on gene expression has yet to receive systematic investigation. 5. The molecular programme elicited by resistance exercise and endurance exercise differs markedly. Muscular hypertrophy following resistance exercise is dependent on the activation of satellite cells and their subsequent myogenic maturation. Endurance exercise requires the simultaneous activation of mitochondrial and nuclear genes to enable mitochondrial biogenesis. 6. Future analysis of the regulation of genes by exercise may combine high-throughput technologies, such as gene-chips, enabling the rapid detection and analysis of changes in the expression of many thousands of genes.

Contribution of circulating acetylcholine to sensory nerve conduction augmentation

We previously discovered that sensory nerve action potential amplitudes increased during isometric muscle contraction and that this response could be blocked with tourniquet isolation of the contraction source. The hypothesis for this study was that a circulating factor was responsible for this effect. In this prospective study, baseline and post intravenous injection of serial sural nerve action potential recordings were made in the leg of 8 rabbits. The sequence of the injections was randomized: 1) normal saline placebo, 2) 0.01 mg/ kg acetylcholine (ACh) 3) 200 mg/ kg Na acetate, 4) 260 mg/ kg Na lactate, and 5) 20 mg/ kg choline. Results showed there was a 3.8 μV increase in the sural nerve response 6 min after ACh injection compared to baseline at rest (p = .01, power = .9, analysis of variance (ANOVA), repeated measures). There were no significant changes in the amplitudes of the sural nerve after injection of the remaining agents or placebo (p = .33 to .81, ANOVA, repeated measures). In conclusion, circulating ACh is the only agent tested thus far that appears to be responsible for this effect. In addition, the amplitude and temporal curve of this response is similar to that seen after exercise in human subjects. The clinical importance of this study is that ACh plays a role in this newly discovered sensory regulatory mechanism controlled by the motor system.

Skeletal muscle substrate metabolism during exercise: methodological considerations.

The aim of the present article is to evaluate critically the various methods employed in studies designed to quantify precisely skeletal muscle substrate utilization during exercise. In general, the pattern of substrate utilization during exercise can be described well from O2 uptake measurements and the respiratory exchange ratio. However, if the aim is to quantify limb or muscle metabolism, invasive measurements have to be carried out, such as the determination of blood flow, arterio-venous (a-v) difference measurements for O2 and relevant substrates, and biopsies of the active muscle. As many substrates and metabolites may be both taken up and released by muscle at rest and during exercise, isotopes can be used to determine uptake and/or release and also fractional uptake can be accounted for. Furthermore, the use of isotopes opens up further possibilities for the estimation of oxidation rates of various substrates. There are several methodological concerns to be aware of when studying the metabolic response to exercise in human subjects. These concerns include: (1) the muscle mass involved in the exercise is largely unknown (bicycle or treadmill). Moreover, whether the muscle sample obtained from a limb muscle and the substrate and metabolite concentrations are representative can be a problem; (2) the placement of the venous catheter can be critical, and it should be secured so that the blood sample represents blood from the active muscle with a minimum of contamination from other muscles and tissues; (3) the use of net limb glycerol release to estimate lipolysis is probably not valid (triacylglycerol utilization by muscle), since glycerol can be metabolized in skeletal muscle; (4) the precision of blood-borne substrate concentrations during exercise measured by a-v difference is hampered since they become very small due to the high blood flow. Recommendations are given in order to obtain more quantitative and conclusive data in studies investigating the regulatory mechanisms for substrate choice by muscle.

Vasoactive substances in the interstitium of contracting skeletal muscle examined by microdialysis.

In the study of the regulation of skeletal muscle blood flow during exercise it is useful to obtain information regarding the concentrations of vasoactive substances in the muscle interstitium, a site where the compounds act on the vascular and skeletal muscle cells. The microdialysis technique is a useful tool for measuring interstitial substances in the muscle at rest and during exercise in human subjects, and the technique can also be used to study the effect of both systemic and local interventions in a specific area of an exercising muscle. Probe recovery, which represents the relative amount of a substance that is diffusing to the dialysis membrane, changes from rest to exercise and can be determined by the internal-standard technique which allows for a relatively high time resolution (min). Furthermore, the use of electrodes at the microdialysis outlet makes it possible to perform continuous measurements of interstitial substances. The present review gives examples of how the microdialysis technique has been applied to study potentially important vasodilators such as adenosine, NO and K+ in human skeletal muscles and highlights areas for future research to establish the functional importance of these compounds.

Limb and skeletal muscle blood flow measurements at rest and during exercise in human subjects.

The aim of the present review is to present techniques used for measuring blood flow in human subjects and advice as to when they may be applicable. Since blood flow is required to estimate substrate fluxes, energy turnover and metabolic rate of skeletal muscle, accurate measurements of blood flow are of extreme importance. Several techniques have therefore been developed to enable estimates to be made of the arterial inflow to, venous outflow from, or local blood flow within the muscle. Regional measurements have been performed using electromagnetic flow meters, plethysmography, indicator methods (e.g. thermodilution and indo-cyanine green dye infusion), ultrasound Doppler, and magnetic resonance velocity imaging. Local estimates have been made using 133Xe clearance, microdialysis, near i.r. spectroscopy, positron emission tomography and laser Doppler. In principle, the aim of the study, the type of interventions and the limitations of each technique determine which method may be most appropriate. Ultrasound Doppler and continuous indo-cyanine green dye infusion gives the most accurate limb blood flow measurements at rest. Moreover, the ultrasound Doppler is unique, as it does not demand a steady-state, and because its high temporal resolution allows detection of normal physiological variations as well as continuous measurements during transitional states such as at onset of and in recovery from exercise. During steady-state exercise thermodilution can be used in addition to indo-cyanine green dye infusion and ultrasound Doppler, where the latter is restricted to exercise modes with a fixed vessel position. Magnetic resonance velocity imaging may in addition be used to determine blood flow within deep single vessels. Positron emission tomography seems to be the most promising tool for local skeletal muscle blood-flow measurements in relation to metabolic activity, although the mode and intensity of exercise will be restricted by the apparatus design.

Changes to the gait initiation programme following a running exercise in human subjects

The question addressed by the present study was whether the programme for gait initiation is fully invariant or can be modified by a prior long duration running exercise. Eight subjects performed a series of gait initiation movements on a force platform in three different speed conditions before and after running on a treadmill (3.3 m/s, 0% slope). Following the running exercise, the first step length and velocity were greater and the double stance phase duration was shorter, while the relationships between the temporal parameters of gait initiation and the velocity of the centre of gravity at the end of the first step were not significantly different. During the anticipation phase, the maximal variation of the ankle joints moment remained significantly correlated with the integrated EMG activity of the Tibialis Anterior after the run. However the displacement of the centre of foot pressure, displayed some post-exercise changes, indicating a modification to the postural part of the gait initiation programme. The greater velocities reached after the running exercise could be explained by a recalibration of gravitational force control, while the invariance of time necessary to reach these velocities showed the rigidity of the initiation gait.