Effective Connectivity of Cortical Sensorimotor Networks During Finger Movement Tasks: A Simultaneous fNIRS, fMRI, EEG Study.

Recently, interest has been growing to understand the underlying dynamic directional relationship between simultaneously activated regions of the brain during motor task performance. Such directionality analysis (or effective connectivity analysis), based on non-invasive electrophysiological (electroencephalography-EEG) and hemodynamic (functional near infrared spectroscopy-fNIRS; and functional magnetic resonance imaging-fMRI) neuroimaging modalities can provide an estimate of the motor task-related information flow from one brain region to another. Since EEG, fNIRS and fMRI modalities achieve different spatial and temporal resolutions of motor-task related activation in the brain, the aim of this study was to determine the effective connectivity of cortico-cortical sensorimotor networks during finger movement tasks measured by each neuroimaging modality. Nine healthy subjects performed right hand finger movement tasks of different complexity (simple finger tapping-FT, simple finger sequence-SFS, and complex finger sequence-CFS). We focused our observations on three cortical regions of interest (ROIs), namely the contralateral sensorimotor cortex (SMC), the contralateral premotor cortex (PMC) and the contralateral dorsolateral prefrontal cortex (DLPFC). We estimated the effective connectivity between these ROIs using conditional Granger causality (GC) analysis determined from the time series signals measured by fMRI (blood oxygenation level-dependent-BOLD), fNIRS (oxygenated-O2Hb and deoxygenated-HHb hemoglobin), and EEG (scalp and source level analysis) neuroimaging modalities. The effective connectivity analysis showed significant bi-directional information flow between the SMC, PMC, and DLPFC as determined by the EEG (scalp and source), fMRI (BOLD) and fNIRS (O2Hb and HHb) modalities for all three motor tasks. However the source level EEG GC values were significantly greater than the other modalities. In addition, only the source level EEG showed a significantly greater forward than backward information flow between the ROIs. This simultaneous fMRI, fNIRS and EEG study has shown through independent GC analysis of the respective time series that a bi-directional effective connectivity occurs within a cortico-cortical sensorimotor network (SMC, PMC and DLPFC) during finger movement tasks.

Impaired oxygen uptake kinetics in the first high-level athlete with Hb Hope: a case study.

Hemoglobin (Hb) Hope is a beta-globin chain variant with reduced oxygen (O2) affinity, known to induce anemia. This usually leads to limitations in O2uptake (VO2) and exercise tolerance. We studied the case of a high-level female athlete with Hb Hope. She had been selected for cross-country races from 13 yrs onward, then was a national junior champion in 400-m race, and finally failed to win any cross-country races as an adult. Hematological analysis revealed normal red blood cell indices and Hb level (12.3 g.dL⁻¹). Incremental exercise showed peak work rate (WR), VO(2max) and gas exchange threshold (GET) within normal ranges for healthy females. Constant WR testing at 90% of GET showed that kinetics of pulmonary VO2included the presence of a slow component. This was in disagreement with the data on VO2kinetics response to exercise intensities below GET. Phase 2 parameters, time constant (τ2, 31 s), time delay (TD2, 39 s), amplitude (A2, 780 ml.min⁻¹), and gain in VO2(ΔVO2 .ΔWR-1, 9.2 ml.min-1.W⁻¹) were within normal ranges. Phase 3 showed a slow component similar to that reported in severe exercise. The absence of anemia and the normality of phase 2 suggested normal O2delivery and oxidative metabolism in exercising muscles. In contrast, phase 3 suggested poor aerobic capacity and limited exercise tolerance. However, the lack of symptoms during testing also suggested that the slow component was due to the specific recruitment of fast-twitch fibers in this former champion athlete with Hb Hope in races requiring mainly anaerobic metabolism.

Similar scaling of contralateral and ipsilateral cortical responses during graded unimanual force generation.

Hemibody movements are strongly considered as being under the control of the contralateral hemisphere of the cerebral cortex. However, some neuroimaging studies have found a bilateral activation of either the primary sensori-motor (SM1) areas or the rostral prefrontal cortex (PFC), during unimanual tasks. More than just bilateral, the activation of these areas was found to be symmetrical in some studies. However, the symmetrical response remains strongly controversial notably for handgrip force generations. We therefore aimed to examine the bilateral SM1 and rostral PFC area activations in response to graded submaximal force generation during a unilateral handgrip task. Fifteen healthy subjects performed 6 levels of force (ranging from 5 to 50% of MVC) during a handgrip task. We concomitantly measured the activation of bilateral SM1 and rostral PFC areas through near-infrared spectroscopy (NIRS) and the electromyographic (EMG) activity of the bilateral flexor digitorum superficialis (FDS) muscles. Symmetrical activation was found over the SM1 areas for all the investigated levels of force. At the highest level of force (i.e., 50% of MVC), the EMG of the passive FDS increased significantly and the ipsilateral rostral PFC activation was found more intense than the corresponding contralateral rostral PFC activation. We suggest that the visuo-guided control of force levels during a handgrip task requires the cross-talk from ipsi- to contralateral SM1 to cope for the relative complexity of the task, similar to that which occurs during complex sequential finger movement. We also propose alternative explanations for the observed symmetrical SM1 activation including (i) the ipsilateral corticospinal tract and (ii) interhemispheric inhibition (IHI) mechanism. The increase in EMG activity over the passive FDS could be associated with a release of IHI at 50% of MVC. Finally, our results suggest that the greater ipsilateral (right) rostral PFC activation may reflect the greater demand of attention required to control the motor output at high levels of force.

Aging effects on electrical and hemodynamic responses in the sensorimotor network during unilateral proximal upper limb functional tasks.

Healthy aging leads to poorer performance in upper limb (UL) daily living movements. Understanding the neural correlates linked with UL functional movements may help to better understand how healthy aging affects motor control. Two non-invasive neuroimaging methods allow for monitoring the movement-related brain activity: functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), respectively based on the hemodynamic response and electrical activity of brain regions. Coupled, they provide a better spatiotemporal mapping. The aim of this study was to evaluate the effect of healthy aging on the bilateral sensorimotor (SM1) activation patterns of functional proximal UL movements. Twenty-one young and 21 old healthy participants realized two unilateral proximal UL movements during: i) a paced reaching target task and ii) a circular steering task to capture the speed-accuracy trade-off. Combined fNIRS-EEG system was synchronised with movement capture system to record SM1 activation while moving. The circular steering task performance was significantly lower for the older group. The rate of increase in hemodynamic response was longer in the older group with no difference on the amplitude of fNIRS signal for the two tasks. The EEG results showed aging related reduction of the alpha-beta rhythms synchronisation but no desynchronisation modification. In conclusion, this study uncovers the age-related changes in brain electrical and hemodynamic response patterns in the bilateral sensorimotor network during two functional proximal UL movements using two complementary neuroimaging methods. This opens up the possibility to utilise combined fNIRS-EEG for monitoring the movement-related neuroplasticity in clinical practice.

Time-dependent effect of acute hypoxia on corticospinal excitability in healthy humans.

Contradictory results regarding the effect of hypoxia on cortex excitability have been reported in healthy subjects, possibly depending on hypoxia exposure duration. We evaluated the effects of 1- and 3-h hypoxia on motor corticospinal excitability, intracortical inhibition, and cortical voluntary activation (VA) using transcranial magnetic stimulation (TMS). TMS to the quadriceps cortex area and femoral nerve electrical stimulations were performed in 14 healthy subjects. Motor-evoked potentials (MEPs at 50-100% maximal voluntary contraction; MVC), recruitment curves (MEPs at 30-100% maximal stimulator power output at 50% MVC), cortical silent periods (CSP), and VA were measured in normoxia and after 1 (n = 12) or 3 (n = 10) h of hypoxia (Fi(O(2)) = 0.12). One-hour hypoxia did not modify any parameters of corticospinal excitability but reduced slightly VA, probably due to the repetition of contractions 1 h apart (96 ± 4% vs. 94 ± 4%; P = 0.03). Conversely, 3-h hypoxia significantly increased 1) MEPs of the quadriceps muscles at all force levels (+26 ± 14%, +24 ± 12%, and +27 ± 17% at 50, 75, and 100% MVC, respectively; P = 0.01) and stimulator power outputs (e.g., +21 ± 14% at 70% maximal power), and 2) CSP at all force levels (+20 ± 18%, +18 ± 19%, and +14 ± 22% at 50, 75, and 100% MVC, respectively; P = 0.02) and stimulator power outputs (e.g., +9 ± 8% at 70% maximal power), but did not modify VA (98 ± 1% vs. 97 ± 3%; P = 0.42). These data demonstrate a time-dependent hypoxia-induced increase in motor corticospinal excitability and intracortical inhibition, without changes in VA. The impact of these cortical changes on physical or psychomotor performances needs to be elucidated to better understand the cerebral effects of hypoxemia.

Increased prefrontal activity during usual walking in aging.

Executive functions are important for successful accomplishment of walking tasks, particularly during a dual task. Over the past few years, several studies investigated prefrontal cortex activity under different walking conditions in older adults with functional near infrared spectroscopy (fNIRS). However, little is known about changes in dorsolateral prefrontal cortex (DLPFC) activity during walking in the early stages of aging. The main objective of this study was to compare changes in DLPFC activity during simple and dual task walking across three different age groups. Twenty-five young (age range = 18-37), twenty-five youngest-old (age range = 55-65), and twenty-five older adults (age range = 67-87) participated in this study. Main results showed that, during simple task walking, older adults had increased DLPFC activity with equivalent walking performance. This increased mainly concerned the right hemisphere. During dual task walking, older adults had increased right DLPFC activity but seemed to have enough resources to maintain their performance during DT walking. This result supports the idea that compensation mechanisms, due to loss of automaticity of walking in aging, appear already during simple task walking. Measuring cortical activity with fNIRS during a simple task walking might be used as valuable indicator for identifying individuals at risk of falling.

An intensive exercise-based training program reduces prefrontal activity during usual walking in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) leads to a progressive loss of locomotor automaticity. Consequently, PD patients rely more on executive resources for the control of gait, resulting in increased prefrontal activity while walking. Exercise-based training programs may improve automaticity of walking and reduce prefrontal activity in this population. This study aimed to assess the effect of an intensive multidisciplinary exercise-based training program on prefrontal activity and gait performance during usual walking in PD patients. METHOD: Fourteen patients (mean age: 67 ± 9; disease duration: 6 ± 5 years; Hoehn and Yahr score: 1.9 ± 0.6) were included in this study. They were assessed in ON stage at three different times at 5-week intervals: two times before the training program (T0 and T1) and once after the training program (T2). Gait performance (stride time, speed, stride length, cadence, and their respective coefficient of variation) and cortical activity in the dorsolateral prefrontal cortex (DLPFC) using functional near infrared spectroscopy (fNIRS) were measured during usual walking. RESULTS: Patients had reduced cortical activity of the DLPFC at T2 compared to T1 (p = 0.003). Patients had shorter stride time at T2 compared to T1 (p = 0.025) and tended to have longer stride length at T2 than at T1 (p = 0.056). CONCLUSION: The training program led to positive effects on prefrontal activity and gait performance. Reduced prefrontal activity during usual walking after training program suggests that patients may have a greater reserve capacity to face more challenging walking conditions. Further studies will investigate the effect of this training on cortical activity during dual-task walking..

Analysis of copy number variation in men with non-obstructive azoospermia.

BACKGROUND: Recent findings demonstrate that single nucleotide variants can cause non-obstructive azoospermia (NOA). In contrast, copy number variants (CNVs) were only analysed in few studies in infertile men. Some have reported a higher prevalence of CNVs in infertile versus fertile men. OBJECTIVES: This study aimed to elucidate if CNVs are associated with NOA. MATERIALS AND METHODS: We performed array-based comparative genomic hybridisation (aCGH) in 37 men with meiotic arrest, 194 men with Sertoli cell-only phenotype, and 21 control men. We filtered our data for deletions affecting genes and prioritised the affected genes according to the literature search. Prevalence of CNVs was compared between all groups. Exome data of 2,030 men were screened to detect further genetic variants in prioritised genes. Modelling was performed for the protein encoded by the novel candidate gene TEKT5 and we stained for TEKT5 in human testicular tissue. RESULTS: We determined the cause of infertility in two individuals with homozygous deletions of SYCE1 and in one individual with a heterozygous deletion of SYCE1 combined with a likely pathogenic missense variant on the second allele. We detected heterozygous deletions affecting MLH3, EIF2B2, SLX4, CLPP and TEKT5, in one subject each. CNVs were not detected more frequently in infertile men compared with controls. DISCUSSION: While SYCE1 and MLH3 encode known meiosis-specific proteins, much less is known about the proteins encoded by the other identified candidate genes, warranting further analyses. We were able to identify the cause of infertility in one out of the 231 infertile men by aCGH and in two men by using exome sequencing data. CONCLUSION: As aCGH and exome sequencing are both expensive methods, combining both in a clinical routine is not an effective strategy. Instead, using CNV calling from exome data has recently become more precise, potentially making aCGH dispensable.

Deficiency of the cysteine protease cathepsin S impairs microvessel growth.

During angiogenesis, microvascular endothelial cells (ECs) secrete proteinases that permit penetration of the vascular basement membrane as well as the interstitial extracellular matrix. This study tested the hypothesis that cathepsin S (Cat S) contributes to angiogenesis. Treatment of cultured ECs with inflammatory cytokines or angiogenic factors stimulated the expression of Cat S, whereas inhibition of Cat S activity reduced microtubule formation by impairing cell invasion. ECs from Cat S-deficient mice showed reduced collagenolytic activity and impaired invasion of collagens type I and IV. Cat S-deficient mice displayed defective microvessel development during wound repair. This abnormal angiogenesis occurred despite normal vascular endothelial growth factor and basic fibroblast growth factor levels, implying an essential role for extracellular matrix degradation by Cat S during microvessel formation. These results demonstrate a novel function of endothelium-derived Cat S in angiogenesis.

Effects of compression tights on calf muscle oxygenation and venous pooling during quiet resting in supine and standing positions.

AIM: We applied near-infrared spectroscopy (NIRS) to evaluate in resting conditions the effects of compression tights (CT) on calf muscle oxygenation and venous pooling compared with Lycra(R) elastic tights (ET) and shorts (no compression) according to the body posture (supine vs standing). METHODS: Twelve sportsmen regularly involved in endurance training volunteered to this study. Their average age, height and weight (+/-SD) were 26.5+/-2.6 years, 177+/-6 cm and 70.1+/-4 kg, respectively. Tissue oxygenation index (TOI), deoxyhemoglobin (HHb), and blood pooling (Hbtot) of the right gastrocnemius medialis were continuously monitored at 2 Hz using a NIRS device (NIRO-300, Hamamatsu Photonics, Japan). A home made transducer was used to measure applied pressure at the interface between skin and clothing over the calf area. Subjects were asked to realize a supine-standing protocol (5 min for each position) by wearing CT, ET or shorts in a counterbalanced order on the same day. RESULTS: HHb and Hbtot concentration changes were significantly lower whereas TOI was significantly higher by wearing CT compared with shorts and ET (P<0.001) as did supine compared to upright postures. The mean pressures applied over the calf were 5.6 and 23.2 mmHg during supine and 5 and 24.1 mmHg during standing for ET and CT, respectively. Pressures were significantly different among clothing according to the following rank order: CT>ET>shorts (P<0.001). CONCLUSIONS: CT compared to ET have positive effects on calf muscle oxygenation and venous pooling in quiet resting positions.

Monocarboxylate transporters, blood lactate removal after supramaximal exercise, and fatigue indexes in humans.

The present study investigated whether muscular monocarboxylate transporter (MCT) 1 and 4 contents are related to the blood lactate removal after supramaximal exercise, fatigue indexes measured during different supramaximal exercises, and muscle oxidative parameters in 15 humans with different training status. Lactate recovery curves were obtained after a 1-min all-out exercise. A biexponential time function was then used to determine the velocity constant of the slow phase (gamma(2)), which denoted the blood lactate removal ability. Fatigue indexes were calculated during 1-min all-out (FI(AO)) and repeated 10-s (FI(Sprint)) cycling sprints. Biopsies were taken from the vastus lateralis muscle. MCT1 and MCT4 contents were quantified by Western blots, and maximal muscle oxidative capacity (V(max)) was evaluated with pyruvate + malate and glutamate + malate as substrates. The results showed that the blood lactate removal ability (i.e., gamma(2)) after a 1-min all-out test was significantly related to MCT1 content (r = 0.70, P < 0.01) but not to MCT4 (r = 0.50, P > 0.05). However, greater MCT1 and MCT4 contents were negatively related with a reduction of blood lactate concentration at the end of 1-min all-out exercise (r = -0.56, and r = -0.61, P < 0.05, respectively). Among skeletal muscle oxidative indexes, we only found a relationship between MCT1 and glutamate + malate V(max) (r = 0.63, P < 0.05). Furthermore, MCT1 content, but not MCT4, was inversely related to FI(AO) (r = -0.54, P < 0.05) and FI(Sprint) (r = -0.58, P < 0.05). We concluded that skeletal muscle MCT1 expression was associated with the velocity constant of net blood lactate removal after a 1-min all-out test and with the fatigue indexes. It is proposed that MCT1 expression may be important for blood lactate removal after supramaximal exercise based on the existence of lactate shuttles and, in turn, in favor of a better tolerance to muscle fatigue.

Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL.

Atherosclerotic coronary heart disease is a common complication of the insulin resistance syndrome that can occur with or without diabetes mellitus. Thiazolidinediones (TZDs), which are insulin-sensitizing antidiabetic agents, can modulate the development of atherosclerosis not only by changing the systemic metabolic conditions associated with insulin resistance but also by exerting direct effects on vascular wall cells that express peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear receptor for TZDs. Here we show that troglitazone, a TZD, significantly inhibited fatty streak lesion formation in apolipoprotein E-knockout mice fed a high-fat diet (en face aortic surface lesion areas were 6.9+/-2.5% vs 12.7+/-4.7%, P<0.05; cross-sectional lesion areas were 191 974+/-102 911 micrometer(2) vs 351 738+/-175 597 micrometer(2), P<0.05; n=10). Troglitazone attenuated hyperinsulinemic hyperglycemia and increased high density lipoprotein cholesterol levels. In the aorta, troglitazone markedly increased the mRNA levels of CD36, a scavenger receptor for oxidized low density lipoprotein, presumably by upregulating its expression, at least in part, in the macrophage foam cells. These results indicate that troglitazone potently inhibits fatty streak lesion formation by modulating both metabolic extracellular environments and arterial wall cell functions.

Cardiorespiratory dynamics to hypoxia at the onset of cycling exercise in male endurance subjects.

AIM: It is well established that altering O2 delivering to contracting skeletal muscle affects human performance. In this respect, a reduced O2 supply (e.g., hypoxia) increases the rate of muscle fatigue. This study aimed to determine the effects of moderate hypoxia and exercise intensity on oxygen uptake (VO2) and cardiac output (CO) kinetics during moderate [below the ventilatory threshold (VT)] and heavy (above VT) constant work rate cycling exercises. METHODS: Eight trained males (age, mean+/-SD, 22+/-3 years; height 182+/-5 cm; body mass 71+/-12 kg) performed at the same relative intensity in normoxic (FIO2=0.21) and hypoxic (FIO2=0.13) conditions moderate and heavy exercises during which pulmonary gas exchange was determined breath-by-breath and CO was monitored beat-by-beat with Doppler echocardiography. RESULTS: The rate of increase (t63%, corresponding to time constant and time delay of a monoexponential response) in CO was significantly faster than that of VO2 in 3 out of 4 experimental conditions (p<0.05). Moreover VO2 kinetics were significantly slowed by hypoxia and speeded by exercise intensity, while CO responses were unaffected by such conditions. A slowed CO response was apparent in hypoxia compared to normoxia (p>0.05) in heavy exercise. CONCLUSIONS: These results suggest an absence of coupling between CO and VO2 kinetics, and that cardiorespiratory O2 delivery is likely different at exercise onset as a function of exercise intensity and FIO2.

A general method for fast multiple sequence alignment.

We have developed a fast heuristic algorithm for multiple sequence alignment which provides near-to-optimal results for sufficiently homologous sequences. The algorithm makes use of the standard dynamic programming procedure by applying it to all pairs of sequences. The resulting score matrices for pair-wise alignment give rise to secondary matrices containing the additional charges imposed by forcing the alignment path to run through a particular vertex. Such a constraint corresponds to slicing the sequences at the positions defining that vertex, and aligning the remaining pairs of prefix and suffix sequences separately. From these secondary matrices, one can compute-for any given family of sequences-suitable positions for cutting all of these sequences simultaneously, thus reducing the problem of aligning a family of n sequences of average length l in a Divide and Conquer fashion to aligning two families of n sequences of approximately half that length. In this paper, we explain the method for the case of 3 sequences in detail, and we demonstrate its potential and its limits by discussing its behaviour for several test families. A generalization for aligning more than 3 sequences is lined out, and some actual alignments constructed by our algorithm for various user-defined parameters are presented.

Preferential pharmacological inhibition of macrophage ACAT increases plaque formation in mouse and rabbit models of atherogenesis.

The cholesteryl ester, foam cell-enriched vulnerable plaque is a principle pharmacological target for reducing athero-thrombosis. Acyl CoA:cholesterol Acyl Transferase (ACAT) catalyzes the esterification of free cholesterol in intestine, liver, adrenal and macrophages, leading in the latter cells to intracellular cholesteryl ester accumulation and foam cell formation in the arterial intima. Previous studies suggested the existence of several isoforms of ACAT with different tissue distribution and this has largely been confirmed by molecular cloning of ACAT-1 and ACAT-2. We developed a series of ACAT inhibitors that preferentially inhibited macrophage ACAT relative to hepatic or intestinal ACAT based on in vitro assays and ex vivo bioavailability studies. Four of these compounds were tested in three models of atherosclerosis at oral doses shown to give sufficient bioavailable monocyte/macrophage ACAT inhibitory activity. In fat-fed C57BL/6 mice, chow fed apo E-/- mice and KHC rabbits, the various ACAT inhibitors had either no effect or increased indices of atherosclerotic foam cell formation. Direct and indirect measurements suggest that the increase in plaque formation may have been related to inhibition of macrophage ACAT possibly leading to cytotoxic effects due to augmented free cholesterol. These results suggest that pharmacological inhibition of macrophage ACAT may not reduce, but actually aggravate, foam cell formation and progression.

The LDL receptor is the major pathway for beta-VLDL uptake by mouse peritoneal macrophages.

In order to determine the contribution of the low density lipoprotein receptor (LDL-R) to the removal of apoB-containing native lipoproteins by macrophages, we compared the uptake of beta-VLDL in peritoneal macrophages (MPM) from wild type mice and mice lacking the LDL-R. The d<1.006 g/ml lipoproteins obtained from apoE deficient mice fed a high fat diet were poorly degraded by macrophages and caused only a slight formation of CE in macrophages from both types of mice. On the other hand, d<1.006 g/ml lipoproteins obtained from LDL-R deficient mice fed a high fat diet, beta-VLDL with apoE, were avidly taken up by and markedly stimulated CE formation in wild type macrophages, but not in macrophages lacking the LDL-R. The degradation of 125I-labeled-apoE-containing beta-VLDL by wild type MPM was poorly inhibited by unlabeled human LDL, and beta-VLDL without apoE had no effects. In conclusion, we propose that the in vitro uptake of native apoE-enriched lipoproteins by murine macrophages is primarily mediated by the LDL receptor and not by other apoE-recognizing receptor systems such as: the LDL receptor related protein, the VLDL receptor or the triglyceride-rich lipoprotein receptor.

Thiazolidinedione- and tumor necrosis factor alpha-induced downregulation of peroxisome proliferator-activated receptor gamma mRNA in differentiated 3T3-L1 adipocytes.

Thiazolidinediones (TZDs) are antidiabetic insulin-sensitizing agents that bind to peroxisome proliferator-activated receptor gamma (PPARgamma) and have potent adipogenic effects on 3T3-L1 preadipocytes. In fully differentiated 3T3-L1 adipocytes, TZDs markedly decreased PPARgamma mRNA levels without reducing the expression of genes that are positively regulated by PPARgamma, such as adipocyte lipid-binding protein 2 (aP2) or lipoprotein lipase-(LPL). PPARgamma mRNA levels were also downregulated by tumor necrosis factor alpha (TNFalpha), an antiadipogenic cytokine. We propose that the downregulation of PPARgamma is not the common denominator of the metabolic effects of TZDs and TNFalpha on mature adipocytes.

Muscle chemoreflex elevates muscle blood flow and O2 uptake at exercise onset in nonischemic human forearm.

We tested the hypothesis that increases in forearm blood flow (FBF) during the adaptive phase at the onset of moderate exercise would allow a more rapid increase in muscle O2 uptake (VO2 mus). Fifteen subjects completed forearm exercise in control (Con) and leg occlusion (Occ) conditions. In Occ, exercise of ischemic calf muscles was performed before the onset of forearm exercise to activate the muscle chemoreflex evoking a 25-mmHg increase in mean arterial pressure that was sustained during forearm exercise. Eight subjects who increased FBF during Occ compared with Con in the adaptation phase by >30 ml/min were considered "responders." For the responders, a higher VO2 mus accompanied the higher FBF only during the adaptive phase of the Occ tests, whereas there was no difference in the baseline or steady-state FBF or VO2 mus between Occ and Con. Supplying more blood flow at the onset of exercise allowed a more rapid increase in VO2 mus supporting our hypothesis that, at least for this type of exercise, O2 supply might be limiting.

Oxygen uptake kinetics during two bouts of heavy cycling separated by fatiguing sprint exercise in humans.

We tested the hypothesis that O(2) uptake (Vo(2)) kinetics at the onset of heavy exercise would be altered in a state of muscle fatigue and prior metabolic acidosis. Eight well-trained cyclists completed two identical bouts of 6-min cycling exercise at >85% of peak Vo(2) separated by three successive bouts of 30 s of sprint cycling. Not only was baseline Vo(2) elevated after prior sprint exercises but also the time constant of phase II Vo(2) kinetics was faster (28.9 +/- 2.4 vs. 22.2 +/- 1.7 s; P < 0.05). CO(2) output (Vco(2)) was significantly reduced throughout the second exercise bout. Subsequently Vo(2) was greater at 3 min and increased less after this after prior sprint exercise. Cardiac output, estimated by impedance cardiography, was significantly higher in the first 2 min of the second heavy exercise bout. Normalized integrated surface electromyography of four leg muscles and normalized mean power frequency were not different between exercise bouts. Vo(2) and Vco(2) kinetic responses to heavy exercise were markedly altered by prior multiple sprint exercises.

Relationships between maximal muscle oxidative capacity and blood lactate removal after supramaximal exercise and fatigue indexes in humans.

The present study investigated whether blood lactate removal after supramaximal exercise and fatigue indexes measured during continuous and intermittent supramaximal exercises are related to the maximal muscle oxidative capacity in humans with different training status. Lactate recovery curves were obtained after a 1-min all-out exercise. A biexponential time function was then used to determine the velocity constant of the slow phase (gamma(2)), which denoted the blood lactate removal ability. Fatigue indexes were calculated during all-out (FI(AO)) and repeated 10-s cycling sprints (FI(Sprint)). Biopsies were taken from the vastus lateralis muscle, and maximal ADP-stimulated mitochondrial respiration (V(max)) was evaluated in an oxygraph cell on saponin-permeabilized muscle fibers with pyruvate + malate and glutamate + malate as substrates. Significant relationships were found between gamma(2) and pyruvate + malate V(max) (r = 0.60, P < 0.05), gamma(2) and glutamate + malate V(max) (r = 0.66, P < 0.01), and gamma(2) and citrate synthase activity (r = 0.76, P < 0.01). In addition, gamma(2), glutamate + malate V(max), and pyruvate + malate V(max) were related to FI(AO) (gamma(2) - FI(AO): r = 0.85; P < 0.01; glutamate + malate V(max) - FI(AO): r = 0.70, P < 0.01; and pyruvate + malate V(max) - FI(AO): r = 0.63, P < 0.01) and FI(Sprint) (gamma(2) - FI(Sprint): r = 0.74, P < 0.01; glutamate + malate V(max) - FI(Sprint): r = 0.64, P < 0.01; and pyruvate + malate V(max) - FI(Sprint): r = 0.46, P < 0.01). In conclusion, these results suggested that the maximal muscle oxidative capacity was related to blood lactate removal ability after a 1-min all-out test. Moreover, maximal muscle oxidative capacity and blood lactate removal ability were associated with the delay in the fatigue observed during continuous and intermittent supramaximal exercises in well-trained subjects.