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Background: Muscle weakness is associated with increased mortality risk in chronic haemodialysis (CHD) patients. Protein energy wasting (PEW) and low physical activity could impair muscle quality and contribute to muscle weakness beyond muscle wasting in these patients. Aim of this study was to assess clinical and biological parameters involved in the reduction of muscle strength of CHD patients., Methods: One hundred and twenty-three CHD patients (80 males, 43 females; 68,8 [57.9-78.8] y.o.) were included in this study. Maximal voluntary force (MVF) of quadriceps was assessed using a belt-stabilized hand-held dynamometer. Muscle quality was evaluated by muscle specific torque, defined as the strength per unit of muscle mass. Muscle mass was estimated using lean tissue index (LTI), skeletal muscle mass (SMM) assessed by bioelectrical impedance analysis and creatinine index (CI). Voorrips questionnaire was used to estimate physical activity. Criteria for the diagnosis of PEW were serum albumin, body mass index < 23 kg/m2, creatinine index < 18.82 mg/kg/d and low dietary protein intake estimated by nPCR < 0.80g/kg/d., Results: MVF was 76.1 [58.2-111.7] N.m. and was associated with CI (β = 5.3 [2.2-8.4], p = 0.001), LTI (β = 2.8 [0.6-5.1], p = 0.013), Voorrips score (β = 17.4 [2.9-31.9], p = 0.02) and serum albumin (β = 1.9 [0.5-3.2], p = 0.006). Only serum albumin (β = 0.09 [0.03-0.15], p = 0.003), Voorrips score (β = 0.8 [0.2-1.5], p = 0.005) and CI (β = 0.2 [0.1-0.3], p<0.001) remained associated with muscle specific torque. Thirty patients have dynapenia defined as impaired MVF with maintained SMM and were younger with high hs-CRP (p = 0.001), PEW criteria (p<0.001) and low Voorrips score (p = 0.001), and reduced dialysis vintage (p<0.046)., Conclusions: Beyond atrophy, physical inactivity and PEW conspire to impair muscle strength and specific torque in CHD patients and could be related to muscle quality., Trial Registration: ClinicalTrials.gov NCT02806089., Competing Interests: The authors have declared that no competing interests exist.

Animal studies have suggested that erythropoietin, besides its well-known hematopoietic effects, can modulate metabolism and prevent fat accumulation. We investigated the effects of repeated injections of recombinant human erythropoietin (EPO) on the balance of substrate oxidation during aerobic exercise in humans. Twelve healthy aerobically trained males received subcutaneously either moderate dose of EPO (50 U/kg, EPO) or saline injections (NaCl 0.9 %, control) three times a week for 4 weeks. Body weight, % fat, maximal aerobic capacity, and substrate utilization during exercise were assessed before and after treatment, while hemoglobin and hematocrit were monitored regularly during the treatment. Carbohydrate and fat oxidation were evaluated via indirect calorimetry, during a submaximal exercise performed at 75 % of the participants' maximal aerobic capacity (V̇(O2max)) for 60 min. Results showed that 4 weeks of EPO treatment significantly enhanced fat oxidation (+56 % in EPO versus -9 % in control) during exercise, independent of its effects on hematological parameters or V̇(O2max). This study shows that EPO can modulate substrate utilization during exercise, leading to enhanced fat utilization and lower use of carbohydrates. This opens new research directions exploring whether systemic EPO levels, in physiological conditions, participate to the modulation of fat oxidation.

This study examined the effects of intermittent hypoxic training (IHT) on skeletal muscle monocarboxylate lactate transporter (MCT) expression and anaerobic performance in trained athletes. Cyclists were assigned to two interventions, either normoxic (N; n = 8; 150 mmHg PIO2) or hypoxic (H; n = 10; ∼3000 m, 100 mmHg PIO2) over a three week training (5×1 h-1h30 x week(-1)) period. Prior to and after training, an incremental exercise test to exhaustion (EXT) was performed in normoxia together with a 2 min time trial (TT). Biopsy samples from the vastus lateralis were analyzed for MCT1 and MCT4 using immuno-blotting techniques. The peak power output (PPO) increased (p<0.05) after training (7.2% and 6.6% for N and H, respectively), but VO2max showed no significant change. The average power output in the TT improved significantly (7.3% and 6.4% for N and H, respectively). No differences were found in MCT1 and MCT4 protein content, before and after the training in either the N or H group. These results indicate there are no additional benefits of IHT when compared to similar normoxic training. Hence, the addition of the hypoxic stimulus on anaerobic performance or MCT expression after a three-week training period is ineffective.

Growth hormone (GH) may stimulate water loss during exercise by activating sweating. This study investigated GH secretion and water loss during sequential cycling and running, taking postural changes into account. The two exercise segments had similar durations and were performed at the same relative intensity to determine their respective contributions to water loss and the plasma volume variation noted in such trials. Eight elite triathletes first performed an incremental cycle test to assess maximal oxygen consumption. Then, the triathletes performed one of two trials in randomized order: constant submaximal cycling followed by treadmill running (C1-R2) or an inversed succession of running followed by cycling (R1-C2). Each segment of both trials was performed for 20 minutes at ∼75% of maximal oxygen consumption. The second trial, reversing the segment order of the first trial, took place two weeks later. During cycling, the triathletes used their own bicycles equipped with a profiled handlebar. Blood sampling (for GH concentrations, plasma viscosity and plasma volume variation) was conducted at rest and after each segment while water loss was estimated from the post- and pre-measures. GH increases were significantly lower in R2 than C2 (72.2±50.1 vs. 164.0±157 ng x ml(-1) x min(-1), respectively; P<0.05). Water loss was significantly lower after C1-R2 than R1-C2 (1105±163 and 1235±153 ml, respectively; P<0.05). Plasma volume variation was significantly negative in C1 and R1 (-6.15±2.0 and -3.16±5.0%, respectively; P<0.05), not significant in C2, and significantly positive for seven subjects in R2 (4.05±3.1%). We concluded that the lower GH increases in R2 may have contributed to the smaller reduction in plasma volume by reducing sweating. Moreover, this lower GH response could be explained by the postural change during the transition from cycling to running. We recommend to pay particular attention to their hydration status during R1 which could limit a potential dehydration during C2.

Aim: To assess whether the severity of obstructive sleep apnoea syndrome (OSAS) is associated with altered fat oxidation (FO) during physical exercise in men with type 2 diabetes (T2DM) and/or the metabolic syndrome (MetS)., Methods: A total of 105 consecutive overweight or/and T2DM male patients were hospitalized for metabolic check-ups including bioimpedancemetry to measure lean body mass (LBM), standardized exercise calorimetry to assess FO, maximum fat oxidation (MFO) and carbohydrate oxidation (CHO), and OSAS screening using respiratory polygraphy. Twenty patients were classified as having severe OSAS, according to the apnoea/hypopnoea index (AHI), with greater than 30 events/h (mean AHI: 45.2±14.3 events/h). They were group-matched for age, BMI, and the presence of T2DM and/or MetS with two other OSAS groups: mild (AHI<15 events/h [n=20]; mean AHI: 8.8±4.5 events/h); and moderate (AHI>15 events/h and<30 events/h [n=20]; mean AHI: 23.7±4.2 events/h)., Results: MFO adjusted for LBM was severely decreased in the severe OSAS group (1.6±1.0 mg.min(-1).kgLM(-1)) compared with the moderate (2.5±0.9 mg.min(-1).kgLM(-1); P=0.008) and mild (2.9±0.8 mg.min(-1).kgLM(-1); P=0.003) groups. All exercise-intensity levels (20%, 30%, 40% and 60% of the theoretical maximum aerobic power) showed reduced FO levels between the severe and mild-to-moderate OSAS groups. However, no differences in CHO were seen at any level of exercise between groups. Pearson's correlation analysis showed that AHI and the oxygen desaturation index were negatively associated with MFO corrected for LBM (r=0.41 and r=0.37, respectively; P<0.005)., Conclusion: OSAS severity is associated with altered FO during exercise., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Two lactate/proton cotransporter isoforms (monocarboxylate transporters, MCT1 and MCT4) are present in the plasma (sarcolemmal) membranes of skeletal muscle. Both isoforms are symports and are involved in both muscle pH and lactate regulation. Accordingly, sarcolemmal MCT isoform expression may play an important role in exercise performance. Acute exercise alters human MCT content, within the first 24 h from the onset of exercise. The regulation of MCT protein expression is complex after acute exercise, since there is not a simple concordance between changes in mRNA abundance and protein levels. In general, exercise produces greater increases in MCT1 than in MCT4 content. Chronic exercise also affects MCT1 and MCT4 content, regardless of the initial fitness of subjects. On the basis of cross-sectional studies, intensity would appear to be the most important factor regulating exercise-induced changes in MCT content. Regulation of skeletal muscle MCT1 and MCT4 content by a variety of stimuli inducing an elevation of lactate level (exercise, hypoxia, nutrition, metabolic perturbations) has been demonstrated. Dissociation between the regulation of MCT content and lactate transport activity has been reported in a number of studies, and changes in MCT content are more common in response to contractile activity, whereas changes in lactate transport capacity typically occur in response to changes in metabolic pathways. Muscle MCT expression is involved in, but is not the sole determinant of, muscle H(+) and lactate anion exchange during physical activity.

Objective: We evaluated the effects of targeted, moderate endurance training on healthcare cost, body composition and fitness in type 2 diabetes patients routinely followed within the French healthcare system., Design and Methods: A total of 25 type 2 diabetic patients was randomly assigned to one of two groups: 13 underwent a training programme (eight sessions, followed by training twice a week for 30-45 minutes at home at the level of the ventilatory threshold [V(T)]); and 12 received their usual routine treatment. Both groups were followed for one year to evaluate healthcare costs, exercise effectiveness and a six-minute walking test., Results: The training prevented loss of maximum aerobic capacity, which decreased slightly in the untrained group (P=0.014), and resulted in a higher maximum power output (P=0.041) and six-minute walking distance (P=0.020). The Voorrips activity score correlated with both V(O2max) (r=0.422, P<0.05) and six-minute walking distance (r=0.446, P<0.05). Changes in V(O2max) were negatively correlated with changes in body weight (r=0.608, P<0.01). Training decreased the insulin-resistance index (HOMA-IR) by 26% (P<0.05). Changes in percentages of fat were correlated to changes in waist circumference (r=0.436, P<0.05). The total healthcare cost was reduced by 50% in the trained group (euro 1.65+/-1 per day versus euro 3.00+/-1.47 per day in the untrained group; P<0.02) due to fewer hospitalizations (P=0.05) and less use of sulphonylureas (P<0.05)., Conclusion: Endurance training at V(T) level prevented the decline in aerobic working capacity seen in untrained diabetics over the study period, and resulted in a marked reduction in healthcare costs due to less treatments and fewer hospitalizations.

Aim: The aim of this work was to quantify the magnitude of changes in insulin sensitivity (S(I)) and glucose effectiveness (S(G)) in response to acute exercise in type 2 diabetic (T2D) patients, as previously studied in non-diabetic subjects., Methods: Seven T2D patients and seven non-diabetic controls participated in the study. Two intravenous glucose tolerance tests (0.5 g/kg) with frequent blood sampling over 180 minutes and mathematical modelling were carried out in a randomized fashion, one at rest and the other immediately following 15 minutes of exercise at 50% of the maximum theoretical heart rate (HR(max)) followed by five minutes at 85% of the HR(max). S(I) and S(G) were calculated using Bergman's minimal model., Results: After exercise, S(I) was increased by 773% (from 0.62+/-0.16 to 5.41+/-1.59 min(-1) x 10(-4)/(microU/mL) and even reached the zone of control values at rest (5.52+/-2.28), whereas S(G) remained unchanged. The disposition index acute insulin response (AIR(G)) x S(I) and the product of fasting insulin (I(B)) x S(I) also increased after exercise., Conclusion: A single bout of exercise at moderate intensity in type 2 diabetics did not improve S(G), but markedly improved the low S(I) values found in these patients, indicating that the acute effects of exercise on S(I) are quantitatively important in the interpretation of training-related S(I) changes and may even be therapeutically useful on their own. Surrogates such as homoeostasis model assessment (HOMA) and quantitative insulin-sensitivity check index (QUICKI) were not sensitive enough to detect this increase in S(I) and should probably be used with caution in the follow-up of exercise protocols in diabetic patients.

Objectives: Among exercise calorimetry tests designed for calculating the respective part of carbohydrates and lipids oxidized at exercise, some use 6 min steps and others use 3 min steps. Is this last method, which has been validated in healthy subjects, still accurate in very sedentary patients, who need more time to reach a steady state in respiratory gas exchanges?, Methods: We compared data obtained with calorimetry (RER and indicators of substrate oxidation) performed on the 2nd-3rd min and the 5th-6th min of each step of a protocol using four 6-min submaximal steps in 17 sedentary subjects (mean age: 51 years) including seven type 2 diabetics and six obese persons., Results: Respiratory exchange ratio (RER) measured with the 3 min steps procedure are well correlated with the 6 min procedure in sedentary patients (r=0.928). However, a Bland-Altman analysis indicated an average underestimation of RER with 3 min steps (-0.0138). Moreover, we observed an average underestimation of carbohydrate oxidation rates of 70.1 mg/min with the 3 min steps procedure. On the contrary, as to lipid oxidation, we measured an average overestimation of 16.2 mg/min. Furthermore, carbohydrate and lipid oxidation rates measured with the 3 min steps procedure are well correlated with the 6 min steps procedure. Moreover, there was an average overestimation of the point at cross over with 3 min steps (+3.29 Watts). For lipox max point (power at which the increase in lipid oxidation induced by the increasing workload reaches a maximum), we observed an average underestimation with 3 min steps (-1.88 Watt). Although the differences between respectively mean values in cross over point and lipox max point between the two protocols are weak, a Bland-Altman analysis indicated more relevant discrepancies in many subjects between the two protocols., Conclusion: In very sedentary patients undergoing such tests for targeting exercise prescription, the 3-min procedure appears to be too short for performing an accurate calorimetry and we rather recommend the protocol using 6-min steps.

The present study was designed to investigate whether a protein hydrolysate enriched in branched chain amino acids and antioxidants, trace and mineral elements, and vitamins would affect performance and fatigue. Eighteen sportsmen underwent testing before and after 28 days supplementation with either treatment in protein hydrolysate or placebo. Testing included exhaustive aerobic and anaerobic exercises with determination of blood lactate concentration through exercise and recovery and antioxidant status, but also measurements of maximal oxidative capacity (V. (max)) and citrate synthase activity (CS) from a resting muscle biopsy. Protein hydrolysate resulted in a significant decrease in fatigue indices, without affecting performances. A significant increase in enzymatic antioxidant and a decrease in oxidative damage were observed at rest after treatment but not with a placebo. Decrease in maximal blood lactate and improvement of blood lactate removal were only observed after protein hydrolysate treatment. Furthermore, CS increased significantly, whereas no change was observed in V. (max). In conclusion, this protein hydrolysate treatment induced adaptations that may promote a decrease in fatigue during exercises, potentially explained by changes in parameters used to represent oxidative damage and antioxidant status at rest and changes in lactate metabolism.

Carbohydrates (CHO) and lipids provide the amount of energy required for physical and chemical reactions inside the human body. The various constraints the body has to resolve explain the use of these two substrates, catabolized via distinct pathways to one common final reaction. In the classic model, three main organs/tissues for substrate fluxes (liver, adipose tissue and skeletal muscle) and one organ regulating main reactions by adaptation of hormonal secretions (endocrine pancreas) are described. From this point of view, the only interactions between CHO and lipid metabolisms are mediated by glycaemic changes via insulin/glucagon ratio (IGR). However, according to recent advances, this concept seems to have a limited validity as it does take into account neither the many other interactions between CHO and lipid metabolism that are likely to occur in addition to the coarse control by IGR, nor the long-term regulation of energy balance, whose description began with the discovery of leptin. Moreover, it does not include the effects of energy expenditure. Therefore, this review focuses on three topics: (i) describe interactions between CHO and lipid metabolism at the level of each tissue and organ implied, via hormonal signaling as well as direct action of nutrients, (ii) integrate fluxes of substrates and signals between those tissues at rest in a global view of the metabolism taking into account short-term and long-term regulating factors and (iii) describe separately, to avoid confusion or extrapolation, the short-term and long-term influence of exercise on these regulation loops.

The regulation of intracellular pH during intense muscle contractions occurs via a number of different transport systems [e.g., monocarboxylate transporters (MCTs)] and via intracellular buffering (beta m(in vitro)). The aim of this study was to investigate the effects of an acute bout of high-intensity exercise on both MCT relative abundance and beta m(in vitro) in humans. Six active women volunteered for this study. Biopsies of the vastus lateralis were obtained at rest and immediately after 45 s of exercise at 200% of maximum O2 uptake. Beta m(in vitro) was determined by titration, and MCT relative abundance was determined in membrane preparations by Western blots. High-intensity exercise was associated with a significant decrease in both MCT1 (-24%) and MCT4 (-26%) and a decrease in beta m(in vitro) (-11%; 135 +/- 3 to 120 +/- 2 micromol H+ x g dry muscle(-1) x pH(-1); P < 0.05). These changes were consistently observed in all subjects, and there was a significant correlation between changes in MCT1 and MCT4 relative abundance (R2 = 0.92; P < 0.05). In conclusion, a single bout of high-intensity exercise decreased both MCT relative abundance in membrane preparations and beta m(in vitro). Until the time course of these changes has been established, researchers should consider the possibility that observed training-induced changes in MCT and beta m(in vitro) may be influenced by the acute effects of the last exercise bout, if the biopsy is taken soon after the completion of the training program. The implications that these findings have for lactate (and H+) transport following acute, exhaustive exercise warrant further investigation.

The effects of concurrent hypoxic/endurance training on mitochondrial respiration in permeabilized fibers in trained athletes were investigated. Eighteen endurance athletes were divided into two training groups: normoxic (Nor, n = 8) and hypoxic (H, n = 10). Three weeks (W1-W3) of endurance training (5 sessions of 1 h to 1 h and 30 min per week) were completed. All training sessions were performed under normoxic [160 Torr inspired Po(2) (Pi(O(2)))] or hypoxic conditions ( approximately 100 Torr Pi(O(2)), approximately 3,000 m) for Nor and H group, respectively, at the same relative intensity. Before and after the training period, an incremental test to exhaustion in normoxia was performed, muscle biopsy samples were taken from the vastus lateralis, and mitochondrial respiration in permeabilized fibers was measured. Peak power output (PPO) increased by 7.2% and 6.6% (P < 0.05) for Nor and H, respectively, whereas maximal O(2) uptake (Vo(2 max)) remained unchanged: 58.1 +/- 0.8 vs. 61.0 +/- 1.2 ml.kg(-1).min(-1) and 58.5 +/- 0.7 vs. 58.3 +/- 0.6 ml.kg(-1).min(-1) for Nor and H, respectively, between pretraining (W0) and posttraining (W4). Maximal ADP-stimulated mitochondrial respiration significantly increased for glutamate + malate (6.27 +/- 0.37 vs. 8.51 +/- 0.33 mumol O(2).min(-1).g dry weight(-1)) and significantly decreased for palmitate + malate (3.88 +/- 0.23 vs. 2.77 +/- 0.08 mumol O(2).min(-1).g dry weight(-1)) in the H group. In contrast, no significant differences were found for the Nor group. The findings demonstrate that 1) a 3-wk training period increased the PPO at sea level without any changes in Vo(2 max), and 2) a 3-wk hypoxic exercise training seems to alter the intrinsic properties of mitochondrial function, i.e., substrate preference.

Insulin resistance which characterises obesity and type 2 diabetes depends on genetic and environmental factors. Sedentarity plays a key role in the development of insulin resistance and skeletal muscle of obese or type 2 diabetes patients shows several abnormalities of carbohydrate and fat metabolism. Exercice training by its beneficial effects on skeletal muscle and particularly on mitochondrial function is efficient to prevent and to treat obesity and type 2 diabetes.

Exercise and lactate usually change blood rheology, particularly red blood cell (RBC) deformability. The effect of lactate on RBC aggregation is unknown. The present study tested the in vivo effects of exercise on both lactate and RBC aggregation and the in vitro effects of lactate on RBC aggregation. Thirteen well trained athletes performed a progressive and maximal exercise test during which blood was sampled at rest, at 50% of maximal exercise, and at maximal exercise. RBC aggregation was assessed with the Myrenne aggregometer which gives two indexes of RBC aggregation: "M" (aggregation during stasis after shearing at 600 s(-1)) and "M1" (facilitated aggregation at low shear rate after shearing at 600 s(-1)). A part of the resting blood sample was also reserved to test the in vitro effects of three lactate concentrations (2, 4 and 10 mM). The lactate solutions were described in a previous study (P. Connes, D. Bouix, G. Py, C. Préfaut, J. Mercier, J.F. Brun and C. Caillaud, Opposite effects of in vitro lactate on erythrocyte deformability in athletes and untrained subjects, Clin. Hemorheol. Microcirc. 31 (2004), 311-318). The results demonstrated that M and M1 were unchanged with exercise and lactate. Therefore, lactate is able to change RBC deformability but not RBC aggregation.

Purpose: The aim of this study was to assess the effect of Ramadan fasting on substrate oxidation in trained athletes during moderate-intensity exercise., Methods: Nine trained men (age: 19+/-2 yr, Height: 1.78+/-0.74 m) were tested on three occasions: during a control period immediately before Ramadan (C), at the end of the first week (Beg-R), and during the fourth week of Ramadan (End-R). On each occasion, they performed submaximal cycle ergometer exercise, with work-rates that were increased progressively (loadings corresponding to 20, 30, 40, 50, 60% of Wmax). Steady-state substrate oxidation was evaluated by indirect calorimetry., Results: Participants showed significant decreases in body mass and body fat at the end of Ramadan, relative to initial control values (P<0.001). The daily food intake was also reduced during Ramadan (P<0.01). Haemoglobin concentrations and hematocrit were significantly higher at the end-Ramadan, both at rest (P<0.001 and P<0.0001 respectively) and after exercise, (P<0.05 and P<0.01 respectively) compared to control measurements made before Ramadan. At the end of Ramadan, our subjects had increased their fat utilization during exercise. The cross-over was observed at a higher intensity at the End-R (35% vs. 30% of Wmax, P<0.001). For the same power output, the Lipox max was also higher at the End-R, compared to control value (265+/-38 vs. 199.1+/-20 mg/min, P<0.001)., Conclusion: Ramadan fasting increases the lipid oxidation of trained athletes during submaximal exercise. The increased fat utilisation may be related to decreases in body mass and body fat content.

Objectives: Exercise is a recommended treatment for type 2 diabetes but the actual pattern of metabolic adaptation to exercise in this disease is poorly known and not taken in account in the protocols used. Metabolic defects involved in the pathways of substrate oxidation were described in type 2 diabetes. We hypothesized that type 2 diabetes, regardless of age, gender, training status and weight, could influence by its own the balance of substrates at exercise., Methods: 30 sedentary type 2 diabetic subjects and 38 sedentary matched control subjects were recruited. We used exercise calorimetry to determine lipid and carbohydrate oxidation rates. We calculated two parameters quantifying the balance of substrates induced by increasing exercise intensity: the maximal lipid oxidation point (PLipoxMax) and the Crossover point (COP), intensity from which the part of carbohydrate utilization providing energy becomes predominant on lipid oxidation., Results: Lipid oxidation was lower in the diabetic group, independent of exercise intensity. PLipoxMax and COP were lower in the diabetic group [PLipoxMax=25.3+/-1.4% vs. 36.6+/-1.7% %Wmax (P<0.0001)] - COP =24.2+/-2.2% vs. 38.8+/-1.9% %Wmax (P<0.0001)., Conclusions: Type 2 diabetes is associated with a decrease in lipid oxidation at exercise and a shift towards a predominance of carbohydrate oxidation for exercise intensities lower than in control subjects. Taking into account these alterations could provide a basis for personalizing training intensity.

Background: The aim of the study was to characterize lipid oxidation at exercise in adults with growth hormone deficiency (GHD) and to evaluate the effect of 6 and 12 months of GH replacement therapy on substrate carbohydrate (CHO) and lipid utilization at exercise., Patients and Measurements: Twenty-five patients with GHD and 40 matched controls participated in the study. Ten of the 25 GH-deficient patients were treated with recombinant GH for 12 months. Anthropometric measurements and exercise calorimetry were performed before and after treatment. Maximal fat oxidation and the crossover point [that is the percentage of the theoretical maximal power (Wmax th) where CHO become the predominant fuel used for oxidation] were determined., Results and Conclusion: The GH-deficient patients exhibited a highly significant shift in the balance of substrate oxidation during exercise, towards a decrease in fat oxidation, and a shift towards lower intensities of the crossover (52 +/- 5.5%vs. 72.6 +/- 6.6% of Wmax th, P < 0.03) and maximal fat oxidation (131.04 +/- 14 vs. 234.4 +/- 30.1 mg/min, P < 0.03) in the GHD and control groups, respectively. However, GH treatment at 6 and 12 months partially reversed this defect, resulting in an increase (+83%, P < 0.001) in the maximal ability to oxidize fat during exercise. These findings are consistent with the hypothesis that a lack of GH reduces the ability to oxidize lipids during exercise and that GH treatment restores this muscular metabolic property.

Aging impairs blood rheology while various training protocols improve it. The purpose of this study was to delineate the respective role of aging and endurance training on blood rheology. Thirty-two subjects [16 middle-aged men: 8 cyclists (MAcy) and 8 sedentary men (MAsed) and 16 young men: 8 cyclists (Ycy) and 8 sedentary men (Ysed)] were compared in this study. Results showed higher red blood cell (RBC) rigidity and aggregability (AFFIBIO), lower RBC disaggregability (AFFIBIO) at middle age than at 25 yr, regardless of training status. However there was no age-related difference in whole blood viscosity at either native or corrected hematocrit, plasma viscosity, hematocrit, and Myrenne aggregation indexes M and M1. Training was associated with a reduced hematocrit in middle age subjects but not in 25 yr old ones. We evidenced no effect of training on red cell rigidity (Dintenfass's Tk index), in whole blood viscosity at either native or corrected hematocrit, and plasma viscosity. Thus, regular cycling at middle age maintains a low hematocrit but does not prevent aging-related increase in red cell rigidity and aggregability. Specific effects of cycling among other sports may explain this specific pattern.

There is a lack of consensus about the biological diagnosis of the overtraining syndrome (OTS). Recently, efforts have been made to standardize its clinical diagnosis (e.g., standardized questionnaires like that of the French consensus group on overtraining of the Société Française de Médecine du Sport-SFMS). We previously reported that the early signs of overtraining (= "overreaching") in elite sportsmen are associated with a hemorheologic pattern (raised hematocrit and plasma viscosity etap) that suggests some degree of reversal of the "autohemodilution" which characterizes fitness, and that the feeling of heavy legs in overtrained athletes is related to higher etap and higher red cell aggregation. We thus investigated on a sample of 48 athletes (age 24 +/- 1 yr), referred for possible diagnosis of overtraining to what extent plasma viscosity is a predictor of OTS. From those 48 athletes 10 had a value of etap in the highest quartile (etap > 1.44 pPa.s) and 8 of them had a diagnosis of overreaching, while in the 38 whose etap was < 1.44 mPa.s there were 20 cases of overreachings. Overt cases of OTS were found in 1 subject of the highest quintile and two in the lowest. Thus the predictive value of etap for early stages (overreaching) or chronicized stages (overtraining syndrome) is as follows: (a) prediction of overreaching: sensitivity 28.57%; specificity 90%; positive predictive value 80%; negative predictive value 47.37%; (b) prediction of chronicized overtraining: sensitivity 2.70%; specificity 18.18%; positive predictive value; 10.00%; negative predictive value 5.26%. These results show that etap is a rather specific, although poorly sensitive predictor of overreaching but has no interest in the diagnosis of the overtraining syndrome itself.

Objective: To investigate whether time interval between meal and exercise alters the balance of substrate oxidation during an exercise bout., Hypothesis: Exercise performed 3-h after meal induces a higher rate of lipid oxidation than when performed only 1-h after meal., Research Methods and Procedures: Eight overweight and obese postmenopausal women (age: 57.4+/-2.4 y; BMI: 31.8+/-2.1 kg m(-2); %FAT: 42.7+/-1.2%, mean+/-s.e.m.) performed two sessions of exercise training at an intensity corresponding to their ' crossover' point of substrate oxidation (COP(ox)). One session was held 1 h after a standardized meal and the other, 3 h after an identical meal on another day. Substrate oxidation was evaluated by indirect calorimetry. Hormonal responses were investigated during exercise., Results: Respiratory exchange ratio values were lower in the 3-h condition, showing higher lipid oxidation during exercise (average difference+38.9+/-2.7 mg min(-1); P<0.001), while mean energy expenditure did not differ. Basal heart rate was reduced in the 3 h compared with the 1-h condition (78+/-5 vs 87+/-5 bpm; P<0.05). Glycemia, lactatemia and insulinemia were reduced when exercise was performed 3 h after meal (P<0.05)., Discussion: When exercise is performed 3 h after meal at an intensity corresponding to the COP(ox), metabolic and hormonal responses are similar to those targeted during the submaximal exercise test performed at fast that we previously proposed to individualize exercise training in the obese.

Increased blood lactate concentration and alterations of substrate utilization have been shown to be partly involved in development of insulin resistance in obese and type 2 diabetic patients. As blood represents the first great distribution space and participates to lactate exchange in whole body, we investigated lactate transport in red blood cells at rest and the potential relationships between elevated blood lactate and substrate utilization in 7 obese controls and 7 obese type 2 diabetic postmenopausal women during an incremental exercise test. Blood samples were collected at rest, 30%, 50%, and 60% of maximal power and at 8 and 20 minutes of recovery time. Baseline lactatemia and its increase during exercise were higher in the diabetic group (P < .05). We found a negative correlation between basal and 30% maximal power lactatemia and 2 indexes of substrate utilization (crossover point: r = -0.79, r = -0.82 and maximal lipid oxidation point: r = -0.83, r = -0.80; P < .05) in diabetic group only. Furthermore, there were positive correlations between the affinity constant, maximal velocity transport, and basal lactate level in diabetic subjects (r = 0.91 and r = 0.73, respectively; P < .05). These results show that the elevation of blood lactate is associated with a greater carbohydrate oxidation in type 2 diabetes, but the mechanisms underlying the alteration of substrate utilization need to be clarified. Furthermore, increased lactate levels cannot be explained by alterations of lactate transport in red blood cells, but it could affect monocarboxylate transporter 1 properties.

To investigate 1) the blood rheological responses to high training volume and 2) the potential effect of these responses on arterial hypoxemia induced during submaximal running and cycling, 10 triathletes performed an incremental cycle test, 20 minutes of running (R), and 20 minutes of cycling (C). All trials were performed at nearly 75 % of VO2max. Hematocrit (H), blood viscosity (etab), plasma viscosity (etapl), index of erythrocyte rigidity (Tk), changes in plasma volume (DeltaPV), pulmonary diffusing capacity (DLco), and arteriolized blood gas (PaO2) were measured before and after each trial. Pulse oxymetry (SpO2) and cardioventilatory data were collected continuously. A significant increase in etab, etapl, and H was noted after R and C with respect to pre-exercise, whereas DeltaPV decreased, with a greater decrease after C. Tk was significantly higher after R than after C. A significantly greater drop in DLco was noted after C compared with R. SpO2 decreased significantly more during R, as did PaO2. We conclude that blood rheological responses are specific to running and cycling. Cycling induced a sharp decrease in plasma volume, which could partially explain the greater DLco alteration. Running was characterized by an increase in Tk, which could be implicated in the severity of the drop in arterial oxygenation observed.

Several studies have suggested that athletes with low hemoglobin saturation during exercise may experience impaired pulmonary blood gas exchange during maximal exercise. Blood viscosity may be implicated in exercise-induced pulmonary hemorrhage in race horses. We hypothesized that blood rheology may contribute to impaired gas exchange and reduced hemoglobin saturation during exercise in humans. A group of 20 highly trained endurance athletes participated in this study, 9 with low hemoglobin saturation during exercise (Low-SpO (2) group) and 11 with normal hemoglobin saturation (High-SpO (2) group). All subjects performed a progressive exercise test conducted to V.O (2max). Venous blood was sampled at rest, 50 % V.O (2max) and maximal exercise. Blood viscosity (etab) was measured at very high shear rate (1000 s (-1)) and 37 degrees C with a falling ball viscometer. The erythrocyte rigidity coefficient, "Tk", was calculated using the Dintenfass equation. At rest, no significant difference in etab was observed between the two groups (3.00 +/- 0.08 mPa . s vs. 3.01 +/- 0.04 mPa . s for the Low-SpO (2) and High-SpO (2) group, respectively). At 50 % V.O (2max) and maximal exercise, etab was higher in Low-SpO (2) (p < 0.01). Tk decreased in High-SpO (2) (p < 0.01) but remained unchanged in the other group during testing. The greater increase in etab in the Low-SpO (2) group during exercise may therefore have been due to the lack of reduction in Tk. As suggested by previous studies, the greater increase in blood viscosity in athletes with low hemoglobin saturation may lead to vascular shear stress. Whether this could impair the blood gas barrier and result in exercise-induced hypoxemia requires further study.

We previously reported in rugbywomen correlations between RBC deformability and the ability to oxidize at exercise more lipids. This surprising finding might of course be spurious, or reflect the importance of the balance of substrates at exercise on baseline parameters that regulate blood rheology. Actually, the capacity of skeletal muscle to utilize either lipid or carbohydrate as fuels strongly influences whole body metabolism both at rest and during exercise. While the healthy skeletal muscle has substantial metabolic flexibility and is able to switch from predominantly lipid o oxidation during fasting or endurance exercise to increased glucose oxidation in conditions of insulin stimulation, obese individuals and those with type 2 diabetes manifest higher lipid oxidation during insulin-stimulated conditions despite lower rates of lipid oxidation during fasting or prolonged exercise. A low ability to oxidize and to periodically deplete triglyceride in muscle is associated with raised blood lipids. In addition, high carbohydrate oxidation rates in the mitochondrion are likely to promote more free radical generation. An increase in either blood lipids or free radicals is likely to induce profound hemorheological effects. We present here hemorheological studies in various populations with the use of exercise calorimetry in order to assess this switch of substrates. These studies further evidence negative correlations between the ability to oxidize lipids at exercise and parameters of blood viscosity. Correlations found between RBC deformability and the ability to oxidize at exercise more lipids may be due to effects of endurance training on lipid oxidation which may in turn modify both lipid metabolism and free radical generation, thus influencing RBC rheology., (Copyright 2004 IOS Press)

Background: We assessed the impact of an exercise and diet program for two weeks in a specialized institute and six weeks at home on body composition and exercise metabolism in obese adolescents., Methods: Fourteen obese adolescents took part in the two-week training course and seven continued exercise and diet at home. The substrate crossover point and the maximal fat oxidation point (Lipox max) were determined before and after the program, using indirect calorimetry. Individualized exercise training at Lipox max was programmed over the two months., Results: At the end of the two-week program, all adolescents showed a decrease in weight (p<0.001). Only the seven subjects who continued exercise training at home showed improved exercise fat use (increased crossover point of 17% +/- 3 (p<0.005) and Lipox max of 12.5% +/- 1.5 (p<0.005))., Conclusion: The teenagers who had performed this targeted regular training for two months exhibit an increase in their ability to oxidize lipids at exercise. This increase is no longer found in those treated by diet alone. The efficiency of this targeted training protocol based on calorimetry for the treatment of teenager obesity will require longer studies on greater samples of subjects.

The maximal lactate steady state (MLSS) is defined as the highest blood lactate concentration (MLSSc) and work load (MLSSw) that can be maintained over time without a continual blood lactate accumulation. A close relationship between endurance sport performance and MLSSw has been reported and the average velocity over a marathon is just below MLSSw. This work rate delineates the low- to high-intensity exercises at which carbohydrates contribute more than 50% of the total energy need and at which the fuel mix switches (crosses over) from predominantly fat to predominantly carbohydrate. The rate of metabolic adenosine triphosphate (ATP) turnover increases as a direct function of metabolic power output and the blood lactate at MLSS represents the highest point in the equilibrium between lactate appearance and disappearance both being equal to the lactate turnover. However, MLSSc has been reported to demonstrate a great variability between individuals (from 2-8 mmol/L) in capillary blood and not to be related to MLSSw. The fate of enhanced lactate clearance in trained individuals has been attributed primarily to oxidation in active muscle and gluconeogenesis in liver. The transport of lactate into and out of the cells is facilitated by monocarboxylate transporters (MCTs) which are transmembrane proteins and which are significantly improved by training. Endurance training increases the expression of MCT1 with intervariable effects on MCT4. The relationship between the concentration of the two MCTs and the performance parameters (i.e. the maximal distance run in 20 minutes) in elite athletes has not yet been reported. However, lactate exchange and removal indirectly estimated with velocity constants of the individual blood lactate recovery has been reported to be related to time to exhaustion at maximal oxygen uptake.

Effects of exercise on erythrocyte aggregation were investigated in 19 elite athletes. High shear rate viscometry (1000 s(-1) evidenced an increase in blood viscosity explained by an increase in hematocrit (+8% p<0.01) and plasma viscosity (+7% p<0.01). Erythrocyte rigidity index and erythrocyte aggregability measured using the Myrenne erythroaggregometer did not change. However, using the laser backscattering technique (SEFAM erythroaggregometer), we observed significant changes in aggregability and desaggregability after 25 min of exercise. The initial aggregation time (TA) decreased by 33% (p<0.01), while the final aggregation time decreased by 13.6% (p<0.01). TA was correlated with aerobic working capacity (r=0.73; p=0.005), which was negatively correlated with blood viscosity at rest (r=-0.57; p=0.043). A significant relationship was observed between TA and the initial fibrinogen levels (r=0.71; p<0.01). The plasma volume contraction during exercise was found to be statistically explained by the water loss proportional to the total work load. Thus, laser backscattering demonstrates an increase in aggregability and a decrease in disaggregability of red cells during exercise, proportional to baseline fibrinogen values.

The aim of this study was to compare circulating levels of growth hormone (GH), IGF-I, and IGF-binding protein (IGFBP)-1 and IGFBP-3 in response to a long-duration endurance exercise in trained vs. sedentary middle-aged males and to determine whether a relationship with glucose homeostasis exists. Seven trained men (Tr) were compared with seven age-matched sedentary men (Sed) during two trials of 60 min of cycling exercise performed below (-VT) and above (+VT) the ventilatory threshold. Insulin sensitivity (S(I)) was higher in Tr than in Sed (P < 0.001). Basal GH, IGF-I, and IGFBP-1 and -3 were higher in Tr (P < 0.05). During +VT, Tr had a threefold higher GH response, whereas their blood glucose level was better maintained (P < 0.05). Basal IGFBP-1 was correlated with S(I) (P < 0.01). These data indicate that endurance training in middle-aged men increased the activity of the GH/IGF-I system and improved glucoregulation both at rest and during high-intensity endurance exercise.

Background: The management of abdominal fat accumulation and metabolic disorders in HIV1-infected patients, by an aerobic training program, is considered., Methods: Seventeen lipodystrophic and 2 dyslipidemic (without body modification) adults were studied before and after 4 months of training. The training load was individualized on a ventilatory threshold basis, determined during a maximal exercise test on cycle ergometer. Total (TAT), Visceral (VAT) and Subcutaneous Adipose Tissue (SAT) were assessed by CT-scan. Total (TC) and High Density Lipoprotein (HDL-C) Cholesterol, Triglycerides (TG), lactate (La), insulin and glucose were measured after a 12-hour-overnight fast. LDL, TC/HDL, TG/HDL, HOMA-insulin resistance index and coronary heart disease (CHD) relative risk (RR(CHD)) were calculated., Results: Besides a significant improvement of aerobic fitness, trained patients exhibited a reduction in TAT (-12.8%, p < 0.001), specially at the visceral level (- 12%, p < 0.01) and in TC, TG and La (- 23%, - 43% and - 19% respectively, p < 0.01). HDL-C was increased (+ 6%, p < 0.01). All these effects were above changes that could be expected by a possible regression to the mean artefact. Both TC/HDL and TG/HDL were reduced (p < 0.01) and the estimated RR(CHD) decreased by approximately 13% (p < 0.01). No significant training effect was observed on the 9 available HOMAs. Significant correlations were found between changes in blood lipid values and baseline measures (r range - 0.55 to - 0.79, p < 0.05), indicating a larger improvement when baseline lipid parameters were higher., Conclusion: Aerobic training reduced visceral fat, lipid disorders, basal blood lactate and CHD markers in HIV patients. Training effects were particularly important for patients with marked dyslipidemia.

Objective: The aim of this study was to investigate whether a high-intensity warm-up at the start of a graded, symptom-limited exercise test would enhance heart rate reserve and thus improve the aerobic performance of orthotopic heart transplant patients., Design: Adrenal and cardiorespiratory responses were compared in 10 orthotopic heart transplant patients who performed two graded, symptom-limited exercise tests on an ergocycle., Results: At the start of the graded, symptom-limited exercise test, high intensity increased the norepinephrine level more than usual intensity between rest and the third minute of exercise. This higher norepinephrine level was followed by a higher heart rate response from the fourth minute of exercise. Heart rate reserve was enhanced during high-intensity exercise, without any significant change in peak oxygen uptake., Conclusions: This specific warm-up enhanced heart rate reserve during a graded, symptom-limited exercise test on an ergocycle. Mechanisms more important than limited heart rate reserve are involved in the limitation of exercise tolerance in orthotopic heart transplant patients.

Purpose: The purpose of this study was to test the hypothesis that carbohydrate (CHO) utilization in middle-aged trained men is increased during hard-intensity exercise and decreased during moderate-intensity exercise in comparison with age-matched sedentary men. We also investigated whether a relationship between CHO utilization and glucose disposal exists., Methods: Seven trained cyclists (Tr) and seven age-matched sedentary men (Sed) underwent an intravenous glucose tolerance test after an overnight fast (minimal model method) to determine their glucose disposal; they also performed two 1-h trials on a cycle ergometer below and above their individual ventilatory threshold (VT). Substrate oxidation was evaluated by indirect calorimetry. Hormonal responses were investigated during exercise., Results: Insulin sensitivity (SI) and glucose effectiveness (Sg) were significantly higher in the Tr group than in the Sed group (P < 0.001, P < 0.03). CHO oxidation was significantly higher in the Tr group than in the Sed group when exercise was performed above VT, whereas CHO oxidation was higher in the Sed group when exercise was performed below VT (P < 0.05). Epinephrine (Epi) response during hard-intensity exercise was higher in the Tr group than in the Sed group (P < 0.01). SI was negatively correlated to CHO oxidation in the Tr group (r = -0.743, P < 0.05)., Conclusion: Endurance training results in increased CHO utilization during hard-intensity exercise and reduced CHO oxidation during moderate-intensity exercise in middle-aged men. During hard-intensity exercise, the increased CHO utilization in middle-aged trained men is associated with a greater response in Epi and is inversely related with SI.

In three separate studies, we have observed that the rise in blood lactate during exercise is correlated to blood viscosity and red cell aggregation. Whether these results were related to an effect of blood rheology on lactate production by muscles or on lactate disappearance remains unknown. The modelling of postexercise lactate kinetics allows a fair evaluation of lactate production by muscles (gamma1) and lactate disappearance (gamma2), the latter being easily measurable with simplified protocols. We thus investigated the relationships between pre- and postexercise blood rheology and gamma2. Ten subjects (2 female and 8 males; age 16-45 yr, weight 62-106.5 kg) exhibiting a wide range of gamma2 (from 2 to 7.7x10(-2) min(-1)) underwent a maximal exercise-test with postexercise calculation of gamma2 with the simplified formula gamma2=0.0724+0.755(Lac8-Lac20)/(Lac8.Deltat)-0.00684Lac20 where Lac8 and Lac20 are lactate concentrations 8 and 10 min after exercise stop at the level of VO2max, as previously reported. During exercise whole blood viscosity eta(b) increased (+15%, p<0.01) due to a rise in hematocrit (p<0.05) and plasma viscosity (+0.08+/-0.03 mPa.s, p<0.05), while red cell rigidity was unchanged. Red cell aggregation (Myrenne M1) increased by 11% (p<0.05). Postexercise M1 (measured at VO2max) was the only hemorheologic parameter correlated to gamma2 (r=-0.697, p=0.037). We find once again a statistical relationship between lactate at exercise and red cell aggregation. Microcirculatory adaptations influenced by red cell aggregation may influence lactate disposal (as reflected by gamma2), adding its effect to that of the balance between carbohydrates and fat oxidation which is the major determinant of blood lactate concentrations at exercise in physiological conditions.

Exercise-induced arterial hypoxemia (EIAH), i.e., a significant drop of O2 arterial partial pressure during sea level exercise, has been shown in both aerobically trained athletes and athletic animal species. The mechanisms potentially involved include ventilation/perfusion inequality and/or pulmonary diffusing capacity limitation. In thoroughbred horses, EIAH is going with pulmonary haemorrhage (EIPH). Stress failure of pulmonary capillaries leading to diffusion limitation has been proposed. Indeed, during intense exercise, the increased cardiac output and blood viscosity combine to rise capillary wall stress. Blood rheology may participate to the increase of VA/Q mismatch and capillary wall stress. High level of hematocrit (Hct) are known to alter blood flow distribution and rise shear stress in pulmonary capillaries. Any change in red blood cells (RBC) deformability may lead to aggregation at low shear rate, in post capillary veinules. There are contrasting data regarding the effects of blood rheology on EIPH in horses, however the large augmentation of hematocrit during exercise may cause vessel wall stress. In humans, greatest increase in hematocrit may participate to EIAH as well as RBC deformability. Today there is no consensus opinion and further studies of blood rheology in athletes is a field of interest.

Design: Growth hormone (GH) has demonstrated water-retaining effects in subjects at rest, whereas other research has indicated that GH may stimulate sweating. Thus, the aim of this study was to investigate the effect of fluid intake on the exercise-induced GH response., Methods: Seven healthy male volunteers (age: 27.4+/-1.3 years, weight: 74.5+/-1.1 kg, height: 179.3+/-2.3 cm) performed a 40-min submaximal rectangular cycling exercise in two different sessions. The first session (Session 1) was performed without water intake, and the second (Session 2) involved the ingestion of spring water (four intakes) corresponding to the volume of water lost during the first session., Results: In session 1, the water loss was 568+/-32 ml. In Session 2, the volume of water loss was not significantly different from the volume of fluid intake (524+/-16 versus 568+/-32 ml respectively). The decrease in plasma volume was significantly reduced in Session 2 (-6.69+/-1.59% versus -11.3+/-1.89%; P<0.05). In Session 1, the GH concentration was significantly lower than that during Session 2 after 25 min (3.04+/-1.05 versus 5.26+/-1.81; P<0.05) and after 40 min (13.7+/-3.55 versus 17.60+/-4.14 ng/ml; P<0.05) of exercise. The total GH response was significantly lower in Session 1 than in Session 2 (136.6+/-39.2 versus 202.4+/-58.9 ng/ml x min; P<0.05)., Conclusions: We conclude that the exercise-induced GH response decreases when exercise is performed without fluid intake.

Hypoglycemia during exercise is a common event due to an unbalance between training volume, nutrition, and external influences such as chronobiology, temperature or altitude, in subjects characterized by an acute and chronic increase in glucose effectiveness and insulin sensitivity. While it is preventable by adequate pre-exercise feeding with carbohydrates, it can also be induced by a prior carbohydrate meal with high glycemic index. Adequate training induces resistance to hypoglycemia via a shift in the balance of oxidized substrates and marked hormonal adaptations, but overtraining, by partially reversing this adaptation, favorizes hypoglycemia. Exercise hypoglycemia is a cause of fatigue or exercise cessation, but also impairs thermoregulatory adaptation and is assumed to fragilize muscles and tendons for traumatic events.

Skeletal muscle is a major site of insulin resistance. In addition to glucose transport, oxidative disposal and storage defects, insulin resistant muscle exhibit many other metabolic abnormalities. After a brief review of insulin resistance determinants, we will focus on muscular abnormalities in obesity and type 2 diabetes. Glucose and lipid metabolism defects will be analysed and their interactions discussed. Exercise can improve many of these muscular abnormalities and the mechanisms underlying exercise-induced benefits have been clarified during the past decades. Therefore, exercise training has proved to be useful in the management of insulin resistant states, i.e. mainly obesity, especially in its truncal distribution, and type 2 diabetes. However, exercise prescription remains poorly codified, and results on glycaemic control are sometimes conflicting. In the last part of this review, we will emphasize the pathophysiological basis for an individualized exercise prescription in insulin resistant subjects.

The aim of this study was to investigate the effects of aging on athletes' cardiorespiratory responses to a brief intense intermittent effort, using the force-velocity test as an exercise model. Twelve young athletes (24.8 +/- 1.3 years) and twelve master athletes (65.1 +/- 1.2 years) with similar heights, body masses, and endurance training schedules participated in this study. They performed both a maximal graded exercise and the force-velocity tests. The force-velocity test consisted of the repetition of 6-second sprints against increasing braking forces with 5-minute recovery periods. None of the subjects presented abnormal electrocardiogram responses to the tests. During the force-velocity test, the heart rate magnitudes of response in all subjects were correlated to the corresponding sprint power output (p < .001), with higher values for the young athletes (p < .001). Both groups had similar systolic blood pressure peaks of response during the force-velocity test. Both groups had similar preexercise and end-of-recovery oxygen consumption (VO2), but the young athletes had higher peaks of response (p < .001). The VO2 magnitudes of response increased during the test (p < .01) in all subjects, with higher values for the young athletes (p < .001). There was a positive correlation between the VO2 magnitude of response and (1) the corresponding sprint power output (R = .58,p < .001) and (2) the corresponding number of sprint repetitions (R = .29, p < .02). The young athletes had higher end-of-recovery and peak carbon dioxide production (VCO2) responses than the master athletes (p < .001). Pulmonary ventilation (V(E)) peaks of response to the sprints were higher in the young athletes (p < .001). There was a positive relation between the V(E) and VCO2 peaks of response (R = 84,p < .001). In both groups the peak heart rate, VO2, VCO2, and V(E) values attained during the force-velocity test represented similar percentages of the maximal values reached at exhaustion of maximal graded exercise. These results showed that aging does not alter the percentage of the cardiorespiratory response to a brief intense intermittent exercise such as the force-velocity test. Moreover, the arterial blood pressure response is not significantly altered, whereas the vasodilatatory response is.

Exercise training is known (1) to enhance the function of the GH-IGF-I system, which has profound effects on body fluid status; (2) to increase blood fluidity. Thus, we investigated during an exercise-test in 39 male elite sportsmen (age 23.7+/-0.72 years; body mass index 23.7+/-0.28 kg/m2) the possible relationships between GH and IGF-I status and the rheological properties of blood. Two correlations indicate a relationship between body hydration and fitness: isometric handgrip strength is correlated with the percentage of extracellular water in total body water (r = 0.432, p = 0.02) and the aerobic working capacity W170 is negatively correlated with hematocrit (r = -0.341, p = 0.039). Water loss during exercise appears to be inversely related to fitness as evaluated by W170 (r = -0.529, p = 0.05), and is positively correlated with the score of signs of overtraining (r = 0.725, p = 0.003) and with the red blood cell aggregation index (r = 0.584, p = 0.036). Finally, while the GH peak value is correlated with the extracellular water volume (r = 0.393, p = 0.02), IGF-I is correlated with blood viscosity (r = 0.546, p = 0.0003), suggesting that when IGF-I values are within the upper quintile (>340 ng/ml) IGF-I may unfavourably affect blood rheology. Among factors of blood viscosity, IGF-I exhibits a borderline correlation (p = 0.05) with "Tk" and the ratio IGF1/IGFBP3 which reflects free circulating IGF-I is correlated with red cell aggregability measured with the Myrenne "M" (r = 0.485, p = 0.014) and S60 (r = 0.396, p = 0.494). These findings confirm the importance of hydration and dehydration as determinants of both blood rheology and exercise performance. Moreover, they suggest that values of IGF-I within the upper quintile are associated with an impairment of blood fluidity, possibly due to a direct effect of IGF-I on red cell deformability and aggregability.

Objectives: To characterize the influence of neurological lesion level on the cardiorespiratory and ventilatory responses of two groups of paraplegic athletes during incremental exercise on a treadmill and in the usual conditions for wheelchair exercise., Methods: Cardioventilatory responses evaluated in two groups of paraplegic wheelchair sportsmen designated as high paraplegic athletes (HPA) and low paraplegic athletes (LPA). After 2 min of data collection at rest and 3 min of warm-up at 4 km x h(-1), treadmill speed was increased by 1 km x h(-1) every minute until exhaustion. During this test, ventilation and its components, as well as respiratory exchanges, were measured breath by breath (C.P.X. Medical Graphics) every minute by taking the mean of the last 20 s of each increment., Results: Spirometric values presented no significant differences between groups. At rest, no significant difference was observed between the two groups for all cardiorespiratory and ventilatory values obtained during the treadmill test. At submaximal exercise, all variables increased with the augmentation in workload. With the exception of R, there were no significant differences in the classic cardiorespiratory parameters (VO2, VCO2, HR, VE) between the two groups of paraplegics. For the ventilatory parameters, we observed significant differences between the two groups, with values of f and It/Trf significantly higher (0.01

The paradox of hematocrit in exercise physiology is that artificially increasing it by autotransfusion or erythropoietin doping improves VO2 max and performance, while in normal conditions there is a strong negative correlation between hematocrit and fitness, due to a training-induced "autohemodilution". We aimed at investigating: (a) which is the physiological range of hematocrit in highly trained professional footballers; (b) what are the characteristics of athletes with high vs low hematocrit? We determined in 77 healthy male footballers the physiological range (mean +/- sd) of hematocrit: 42.3+/-2.74, (range -2sigma/+2sigma = 36.8-47.8%) thus defining boundaries of quintiles of distribution for this parameter: 40, 41.6, 42.9, 44.6. In another sample of 42 male footballers we compared three groups: lowest quintile (n = 8), highest quintile (n = 5) and the three middle quintiles considered together (n = 29). Athletes in the lowest quintile compared to those in the four other quintiles had a lower value of blood viscosity (-8%, p < 0.01) but this difference disappeared after correction for hematocrit. These subjects with low hematocrit had also higher values of the following parameters: aerobic working capacity (p < 0.01); isometric adductor strength (p = 0.02); crossover point of carbohydrate oxidation (70% carbohydrates/30% lipids) (p < 0.05); insulin like growth factor binding protein 1 (p < 0.0001). Athletes in the highest quintile had higher red cell aggregability (Myrenne index "M1" 8.45+/-0.38 vs 6.82+/-0.62, p < 0.04) and a higher disaggregability threshold gammaD (72.6+/-22.63 vs 44.49+/-1.37, p < 0.01) and a lower percentage of water in fat-free mass (p < 0.02). On the whole sample hematocrit was negatively correlated with aerobic working capacity (W170 r = -0.329, p = 0.007; Wmax (% of expected value) r = -0.552, p = 0.008; VO2 max (% of expected value) r = -0.543, p = 0.009) and with ferritin (r = -0.33, p = 0.031), and positively correlated with the overtraining score (r = 0.352, p = 0.019) which was in turn negatively correlated with ferritin r = -0.312, p = 0.02). Besides, hematocrit behaves as a major determinant of blood viscosity (correlation with blood viscosity r = 0.997, p < 10(-7)) and erythrocyte disaggregability gammaD (r = 0.384, p = 0.03), but the hematocrit/viscosity ratio (h/eta index of O2 delivery) remains maintained almost constant over the range of values studied. These results show that (a) physiological values of hematocrit in these athletes are comprised between 36 and 48%; (b) "low" hematocrit (<40%) was associated with a higher aerobic capacity; (c) subjects with the higher hematocrits (>44.6%) were frequently overtrained and/or iron-deficient, and their blood viscosity (and red cell disaggregability) tended to be increased.

A standardized questionnaire has been proposed by the French consensus group on overtraining of the Société Française de Médecine du Sport (SFMS) and allows the calculation of a 'score' that may help to quantify the early clinical symptoms of the overtraining syndrome in sportsmen submitted to a heavy training program. We investigated a possible relationship between this score and blood rheology in 36 male elite sportsmen (national level in football, volleyball and karate; age: 17-33 yr) who underwent a standardized check-up including biological measurements and an exercise-test. The overtraining score ranged between 0 and 21 items and was correlated with blood viscosity (r = 0.413, p < 0.02). This correlation was explained by a correlation of this score with plasma viscosity (r = 0.512, p < 0.01) and hematocrit (r = 0.387, p < 0.05). When subjects with a high score (>6) were compared to subjects with a lower score they appeared to have a higher blood viscosity at native (but not corrected) hematocrit (3.18 +/- 0.01 vs. 2.89 +/- 0.05 mPa.s, p < 0.02), explained by higher values in both plasma viscosity (1.39 +/- 0.02 vs. 1.31 +/- 0.02 mPa.s, p < 0.01) and hematocrit (42.8 +/- 0.45 vs. 41.1 +/- 0.44, p < 0.05). By contrast, there was no difference in RBC deformability and aggregation. Overtrained subjects have also lower levels of zinc (0.72 +/- 0.024 vs. 0.84 +/- 0.023 mg/l, p < 0.01), ferritin (55.1 +/- 7.3 vs. 92.3 +/- 9.4 ng/ml), and IGF-binding protein 3 (3.4 +/- 0.22 vs. 4.52 +/- 0.4 ng/ml). Neither zinc nor ferritin status were likely to explain the rheologic alterations since disturbances in zinc or iron are rather associated with abnormalities in erythrocyte deformability or aggregability. Therefore, the early signs of overtraining in elite sportsmen are associated with a hemorheologic pattern that suggests some degree of reversal of the 'autohemodilution' associated with fitness in athletes.

We investigated whether localized 1H nuclear magnetic resonance spectroscopy (NMRS) using stimulated echoes (STEAM) with a long mixing time (t(m)) allowed the suppression of the fat signal and detection of lactate in skeletal muscle. The 1H NMRS sequence was first validated in three isolated and perfused rabbit biceps brachii muscles. Spectra were obtained on a wide-bore spectrometer using a dual-tuned probe (1H and 31P). Death was simulated by ceasing the muscle perfusion, which allowed post-mortem changes to be followed. During and after the simulated death, changes in levels of pH and in content of energy-rich compounds were observed with 31P NMRS. Our results showed an inverse linear relationship between pH and lactate in each of the three rabbits (r = 0.93, P < 0.001; r = 0.92, P < 0.01; r = 0.89, P < 0.01) and a decrease in phosphocreatine and concomitant increase in lactate. We then investigated whether this sequence allowed repeated detection of lactate in human soleus muscle during the recovery between periods of intense exercise (force-velocity test, F-v test). Seven subjects mean age 25.1 (SEM 0.8) years participated in this study. Soleus muscle lactate was detected at rest and for 3 min 30 s of the 5-min recovery between periods using a 2.35-T 40-cm bore magnet spectrometer. Arm venous plasma lactate concentration was measured at rest, during the F-v test when the subject stopped pedalling (S1), and at the end of each 5-min recovery between periods (S2). Results showed that the venous plasma lactate concentration at S1 and S2 increased significantly from the beginning of the F-v test to peak anaerobic power (W(an,peak)) (P < 0.001). The spectra showed that muscle lactate resonance intensity rose markedly when W(an,peak) was achieved. The muscle lactate resonance intensity plotted as a percentage of the resting value increased significantly at W(an,peak) compared with submaximal braking forces (P < 0.05). We concluded from these results that localized 1H NMRS using STEAM with a long t(m) allows suppression of the fat signal and repeated detection of lactate on isolated perfused skeletal muscle in animals and between periods of intense exercise in humans.

The aim of the present study was to assess blood lactate concentrations ([LA], mmol x L(-1)) and oxygen uptake (VO2, L x min(-1), mL x kg(-1) x min(-1)) during incremental exercise in subjects with sickle cell trait (SCT) only, i.e., sedentary subjects with SCT without anemia and/or associated alpha thalassemia. Anemia was ruled out using hemoglobin (Hb) level, and alphathalassemia was ruled out using hemoglobin S (HbS) percentage and concomitant Hb level and mean corpuscular volume (MCV). Comparison was made with control subjects with normal Hb, matched for physical fitness, anthropometric data, and hematological parameters. All subjects underwent an incremental exercise test (IET) using an electromagnetic cycle ergometer. Ventilatory data, i.e., minute ventilation (VE, L x min(-1)), oxygen uptake (VO2, mL x min(-1), mL x Kg(-1) x min(-1)) carbon dioxide production (VO2, mL x min(-1)), ventilatory equivalent for O2(VE x VO2(-1))and for CO2 (VE x VO2(-1)), and respiratory exchange ratio (RER, VO2 x VO2(-1)), were collected every minute during IET and the recovery period using a breath-by-breath automated system. Heart rate (HR, beats x min(-1)) was measured every minute using an EKG. Blood sampling was done every minute during IET and the first 5 min of the recovery period, and then every 5 min until the 20th minute of recovery. [LA] were determined by an enzymatic method with a spectrophotometer. Comparisons of all mean cardioventilatory variables showed no significant differences in subjects with SCT versus controls during IET and recovery. In contrast, analysis of variance revealed significantly lower time courses of [LA] during IET (P < 0.05) and recovery (P < 0.05), whereas time courses of VO2 were similar (P > 0.05). We conclude that the lower [LA] exhibited by subjects with SCT during incremental exercise and the subsequent recovery was not associated with concomitant oxygen uptake impairment.

We investigated metabolic and hormonal responses during repeated bouts of brief and intense exercise (a force-velocity test; Fv test) and examined the effect of glucose ingestion on these responses and on exercise performance. The test was performed twice by seven subjects [27 (2) years] according to a double-blind randomized crossover protocol. During the experimental trial (GLU), the subjects ingested 500 ml of glucose polymer solution containing 25 g glucose 15 min before starting the exercise. During the control trial (CON), the subjects received an equal volume of sweet placebo (aspartame). Exercise performance was assessed by calculating peak anaerobic power (W(an,peak)). Venous plasma lactate concentration increased significantly during the Fv test (P < 0.001), but no difference was found between CON and GLU. Blood glucose first decreased significantly from the beginning of exercise up to the 6-kg load (P < 0.001) and then increased significantly at W(an,peak) and for up to 10 min during the recovery period (P < 0.001) in both CON and GLU. Insulin concentrations decreased significantly in both groups, but were higher at W(an,peak) in GLU compared with CON (P < 0.05). Glucagon and epinephrine did not change significantly in either group, but epinephrine was significantly lower in GLU after glucose ingestion (P < 0.05) and at W(an,peak) (P < 0.05). W(an,peak) was not significantly different between CON and GLU. In conclusion, blood glucose and insulin concentrations decreased during repeated bouts of brief and intense exercise, while blood lactate concentration increased markedly without any significant change in glucagon and epinephrine concentrations. Glucose ingestion altered metabolic and hormonal responses during the Fv test, but the performance as measured by W(an,peak) was not changed.

The aims of the present study were: (1) to assess aerobic metabolism in paraplegic (P) athletes (spinal lesion level, T4-L3) by means of peak oxygen uptake (VO2peak) and ventilatory threshold (VT), and (2) to determine the nature of exercise limitation in these athletes by means of cardioventilatory responses at peak exercise. Eight P athletes underwent conventional spirographic measurements and then performed an incremental wheelchair exercise on an adapted treadmill. Ventilatory data were collected every minute using an automated metabolic system: ventilation (l x min[-1]), oxygen uptake (VO2, l x min[-1], ml x min[-1] x kg[-1]), carbon dioxide production (VCO2, ml x min[-1]), respiratory exchange ratio, breathing frequency and tidal volume. Heart rate (HR, beats x min[-1]) was collected with the aid of a standard electrocardiogram. VO2peak was determined using conventional criteria. VT was determined by the breakpoint in the VCO2 - VO2 relationship, and is expressed as the absolute VT (VO2, ml x min[-1] x kg[-1]) and relative VT (percentage of VO2peak). Spirometric values and cardioventilatory responses at rest and at peak exercise allowed the measurement of ventilatory reserve (VR), heart rate reserve (HRr), heart rate response (HRR), and O2 pulse (O2 P). Results showed a VO2peak value of 40.6 (2.5) ml x min(-1) x kg(-1), an absolute VT detected at 23.1 (1.5) ml x min(-1) x kg(-1) VO2 and a relative VT at 56.4 (2.2)% VO2peak. HRr [15.8 (3.2) beats min(-1)], HRR [48.6 (4.3) beat x l(-1)], and O2 P [0.23 (0.02) ml x kg(-1) x beat(-1)] were normal, whereas VR at peak exercise [42.7 (2.4)%] was increased. As wheelchair exercise excluded the use of an able-bodied (AB) control group, we compared our VO2peak and VT results with those for other P subjects and AB controls reported in the literature, and we compared our cardioventilatory responses with those for respiratory and cardiac patients. The low VO2peak values obtained compared with subject values obtained during an arm-crank exercise may be due to a reduced active muscle mass. Absolute VT was somewhat comparable to that of AB subjects, mainly due to the similar muscle mass involved in wheelchair and arm-crank exercise by P and AB subjects, respectively. The increased VR, as reported in patients with chronic heart failure, suggested that P athletes exhibited cardiac limitation at peak exercise, and this contributed to the lower VO2peak measured in these subjects.

We investigated NaHCO3 infusion effects on plasma lactate removal by forearm muscles and performance during intensive leg exercise. Seven subjects performed the force-velocity (FV) test with placebo and NaHCO3 (2 mEq.min-1) with a double-blind crossover protocol. Blood samples for arterial ([LA]A) and venous ([LA]V) lactate determinations were taken 1) at rest before infusion, and 2, 6, 10, 14, 18, and 22 min following its start; and 2) at the end of each exercise bout. The arteriovenous difference ([LA]A-V) was determined for each sampling. NaHCO3 significantly increased arterial bicarbonate concentration and pH during rest (P < 0.001; P < 0.001) and the FV test (P < 0.001; P < 0.05). During the test, [LA]A and [LA]V were significantly higher with NaHCO3 (P < 0.05, P < 0.001). At test onset, [LA]A-V became positive and increased until the braking force of 6 kg, with NaHCO3 and placebo, with values significantly lower for NaHCO3 (P < 0.001). Peak anaerobic power (Wanae, peak) and the corresponding braking force (Fmax) were also determined. Fmax was significantly increased with NaHCO3 (P < 0.001). In conclusion, the increasing rise in [LA]A and [LA]V induced by NaHCO3 may be partly explained by a decreased rate of lactate uptake by forearm skeletal muscles. NaHCO3 did not improve Wanae, peak, but improved Fmax, thus increasing FV duration.

The pathophysiological process of exercise-induced death in subjects with sickle cell trait (SCT) remains unclear. Concerning the cause of death, authors have suggested stressful environmental conditions such as altitude, heat and humidity, or abnormal patient conditions such as deconditioning, fatigue, and disease. These conditions are thought to lead to hypoxemia, hyperlactatemia, acidosis, dehydration, hyperthermia, or exercise-induced rhabdomyolysis, all of which may initiate sickle cell crisis, disseminated intravascular coagulation, myoglobinuria, and renal failure. We report the case of a 41-yr-old, healthy, and apparently well-conditioned subject with SCT who died during a cross-country race under normal environmental conditions in good weather (in terms of temperature and humidity). The medical and athletic history of the subject were unremarkable. We refer to an epidemiological study that reported a relation between age and exercise-induced sudden death in subjects with SCT. We then review the pathophysiological effects of aging in association with deconditioning and high-level training reported in the literature, particularly the decrease in aerobic metabolism in deconditioned subjects, and the exercise-induced hypoxemia in highly trained subjects. We discuss the consequences of deconditioning and high-level training in subjects with SCT during exercise, and conclude that these factors may be involved in the age-dependent risk of exercise-related sudden death in subjects with SCT.