Biomedical subjects

Jacques Mercier

Publications and source records attributed to Jacques Mercier.

32 records · Page 2Linked to original sources

PubMed2004

Injections of recombinant human erythropoietin increases lactate influx into erythrocytes.

Previous studies showed that erythropoietin not only increases erythrocyte production but is also essential in both the synthesis and the good functioning of several erythrocyte membrane proteins, including band 3. It is still unknown whether anion and/or H(+) fluxes are modified by erythropoietin. This study aimed to evaluate the effect of recombinant human erythropoietin (rHuEPO) injections on lactate transport into erythrocytes via band 3 and H(+)-monocarboxylate transporter MCT-1, two proteins involved in lactate exchange. Nine athletes received subcutaneous rHuEPO (50 U/kg body mass 3 times a week for 4 wk), and seven athletes received a saline solution (placebo group). All subjects were also supplemented with oral iron and vitamins B(9) and B(12). Lactate transport into erythrocytes was studied before and after the rHuEPO treatment at different lactate concentrations (1.6, 8.1, 41, and 81.1 mM). After treatment, MCT-1 lactate uptake was increased at 1.6, 41 (P < 0.01), and 81.1 mM lactate concentration (P < 0.001) although lactate uptake via band 3 and nonionic diffusion were unchanged. MCT-1 maximal velocity increased in the rHuEPO group (P < 0.05), reaching higher values than in the placebo group (P < 0.05) after treatment. Our results show that rHuEPO injections increased MCT-1 lactate influx at low and high lactate concentrations. The increase in MCT-1 maximal velocity suggests that rHuEPO may stimulate MCT-1 synthesis during erythrocyte formation in bone marrow.

Adult↗

PubMed2004

Nutrition as a determinant of blood rheology and fibrinogen in athletes.

Blood rheology is influenced by metabolism and nutrition. We investigated this issue in 41 elite athletes exercising 13+/-0.9 hr/wk (mean age: 23.9+/-0.67 yr; mean VO2max: 52.6+/-2.3 ml/min/kg body weight) with a standardised nutritional questionnaire suitable for sports medicine. Calorie intake (% of recommended intake) was negatively correlated with the RBC disaggregability threshold (r=-0.505, p=0.01). There were negative correlations between fibrinogen and protein intake (% of the total caloric intake r=-0.787, p=0.0008; amount in g/kg/day r=-0.597, p=0.03). Accordingly, the RBC disaggregability threshold was also correlated negatively with protein intake (r=-0.508, p=0.05). Lipid intake (g/kg/day) was negatively correlated with the RBC disaggregability threshold (r=-0.564, p=0.03) and positively to the hematocrit/viscosity ratio (r=0.531, p=0.03). Carbohydrate intake (g/kg/day) was positively correlated with whole blood viscosity (r=0.517, p=0.04) and negatively to the hematocrit/viscosity ratio (r=-0.4863, p=0.05). In addition fibrinogen was negatively correlated with hematocrit (r=-0.4129, p=0.036) and positively with a host of aggregation parameters (p<0.001). Therefore fibrinogen levels and red cell rheology exhibit correlations with the nutritional status in athletes. Low protein intake appears to be associated with (mildly) raised fibrinogen and aggregability, and low calorie intake is associated with lower RBC disaggregability.

Adult↗

PubMed2004

Blood fluidity is related to the ability to oxidize lipids at exercise.

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.

Erythrocyte Aggregation↗

PubMed2004

Opposite effects of in vitro lactate on erythrocyte deformability in athletes and untrained subjects.

Exercise transiently increases blood viscosity: however data on red cell deformability in this process remain inconsistent, since studies report either impairment (proportional to blood lactate accumulation), a lack of effect, or even in some cases an improvement. To test whether these inconsistencies may be due to physiological differences among populations studied, we compared the effects of in vitro lactate (2 mM, 4 mM and 10 mM) on erythrocyte rigidity in venous blood drawn at rest in 10 untrained vs 10 aerobically-trained subjects. After adjustment of osmolality and pH and incubation at 37 degrees C during 2 minutes, viscometric measurements were performed at 1000 s-1 with the MT90 (falling ball) viscometer and Dintenfass's 'Tk' was calculated. While at baseline there was no significant difference in Tk between the two groups, it decreased in the aerobically-trained subjects between 2 and 10 mM lactate concentrations (p<0.05) and increased in the untrained group between 2 and 4 mM (p<0.05). Thus, it seems that endurance training influences erythrocyte response to lactate. Lactate impaired erythrocyte deformability in untrained subjects but it (unexpectedly) improved it in trained subjects. This difference may be due to training-induced adaptations in erythrocyte metabolism, possibly including transmembrane transfer via monocarboxylate transporters.

Adaptation, Physiological↗

PubMed2003

Effects of the order of running and cycling of similar intensity and duration on pulmonary diffusing capacity in triathletes.

To study the pathophysiological mechanisms involved in the decrease of post-triathlon diffusing capacity (DLco), blood rheologic properties (blood viscosity: eta(b); changes in plasma volume: deltaPV) and atrial natriuretic factor (ANF) were assessed in ten triathletes during cycle-run (CR) and run-cycle (RC) trials at a metabolic intensity of 75% of maximal oxygen consumption ( VO(2max)). The DLco was measured before and 10 min after trials. ANF and deltaPV were measured at rest, after the cycle and run of CR and RC trials, and at the end of and 10 min after exercise. RC led to a greater deltaDLco decrease, a lower ANF concentration and a lower deltaPV than did CR, whereas for both CR and RC eta(b) was increased throughout exercise and 10 min after. In addition, after CR the deltaDLco decrease was inversely correlated ( r=-0.764; P<0.01) with deltaPV. The association of decreased plasma volume, increased eta(b), and lower ANF concentrations after RC suggested that lower blood pulmonary volume may have caused the greater decrease in Dlco as compared with CR. The inverse correlation between deltaPV and deltaDLco reinforces the hypothesis that fluid shifts limit the post-exercise DLco decrease after the CR succession in triathletes. Lastly, cycling in the crouched position might increase intra-thoracic pressure, decrease thorax volume due to the forearm position on the handlebars, and weaken peripheral muscular pump efficacy, all of which would limit venous return to the heart, and thus result in low pulmonary blood volume. Compared with cycling, running appeared to induce the opposite effects.

Adult↗

PubMed2003

The concept of maximal lactate steady state: a bridge between biochemistry, physiology and sport science.

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.

Adaptation, Physiological↗

PubMed2002

Effects of prolonged mechanical ventilation on respiratory muscle ultrastructure and mitochondrial respiration in rabbits.

OBJECTIVE: To investigate in rabbits whether prolonged mechanical ventilation (PMV) leads to ultrastructural changes in respiratory muscles and alters diaphragm mitochondrial respiration. DESIGN AND SETTING: Experimental prospective study in a university laboratory. ANIMALS AND INTERVENTIONS: We studied respiratory muscles of seven rabbits after 49+/-1 h of controlled mechanical ventilation. Ten nonventilated rabbits were used as a control group. MEASUREMENTS AND RESULTS: After mechanical ventilation electron-microscopic observations of the diaphragm and the external intercostal muscles revealed disrupted myofibrils, increased number of lipid vacuoles in the sarcoplasm, and smaller mitochondria with focal membrane disruptions. Volumetric and numerical densities of the mitochondria were significantly lower in the PMV group than the control group. Mitochondrial respiration was quantified in isolated diaphragm muscle-cell mitochondria using two respiratory substrates. There was no difference in oxygen consumption values in the three states of mitochondrial respiration between the two groups except for state 2 (basal state) with pyruvate/malate parameter (53.5+/-20 for the ventilated group vs. 33.8+/-10.2 nmol atom O/mg per minute for the control group). There was no significant difference between groups in ADP/O ratio or respiratory control ratio. CONCLUSIONS: PMV leads to respiratory muscle cell degeneration and minor changes in oxidative phosphorylation coupling in diaphragmatic mitochondria. These phenomena may mediate part of damage of respiratory muscles after inactivity related to PMV.

Animals↗

PubMed2002

Effects of streptozotocin-induced diabetes on markers of skeletal muscle metabolism and monocarboxylate transporter 1 to monocarboxylate transporter 4 transporters.

Diabetes is known to alter both oxidative and glycolytic pathways in a fiber type-dependent manner. In various skeletal muscles of normal rats, monocarboxylate transporter 1 (MCT1) has been found to be highly correlated to lactate uptake, as well as to oxidative capacity, whereas the distribution and characteristics of MCT4 make it a good candidate for the extrusion of lactic acid from glycolytic muscle cells. Since a previous study found decreased sarcolemmal lactate uptake in streptozotocin (STZ)-diabetic rats, we investigated the presence of MCT1 in relation to enzymatic markers of both oxidative and glycolytic pathways, as well as MCT4 content, in STZ-diabetic rats. Soleus (SOL), red tibialis anterior (RTA), extensor digitorus longus (EDL), heart, and preparations of purified sarcolemmal vesicles (SV) from control and STZ-diabetic rats were harvested for MCT1 and MCT4 content, citrate synthase activity (CS), and lactate dehydrogenase (LDH) isozymes. Basal blood lactate concentration was increased by 38% in the diabetic rats (close to 1.91 mmol/L). However, no change was found in either MCT1 or MCT4 content in these rats. The diabetic rats presented fiber type-specific decrease in CS activity. We noted a redistribution in LDH isozymes in diabetic muscles with a general increase in type H-LDH. Regression analyses indicated (1) a strong relationship between LDH-4 and LDH-5 and (2) MCT1 was still correlated with CS activity in diabetic muscles. These results suggest that diabetes-induced hyperlactatemia is not associated with changes in MCT1 or MCT4 expression, but with alterations of oxidative and glycolytic enzymes.

Animals↗

PubMed2002

Management of dental extractions in patients with bleeding disorders.

OBJECTIVE: This study evaluated the effectiveness of a protocol to prevent bleeding after dental extraction in patients with hemophilia, von Willebrand's disease (VWD), or platelet disorders. STUDY DESIGN: Replacement therapy was used in cases involving general anesthesia, and nerve trunk infiltration was used in patients with severe bleeding disorders (severe-to-moderate hemophilia or type 2-3 VWD). Desmopressin was used in good responders with mild hemophilia A, type 1 VWD, and platelet disorders. Local hemostatic measures and antifibrinolytic treatment were used systematically. RESULTS: Ninety-three patients underwent 103 dental extractions; 2 of these patients had secondary bleeding requiring surgical hemostasis. CONCLUSION: The indication for replacement therapy depended on the type of anesthesia that was used. Coagulation factor concentrates or desmopressin were necessary to avoid upper airway hematoma with general anesthesia or nerve trunk infiltration. With local anesthesia, substitutive treatment was indicated in patients with severe-to-moderate hemophilia and type 2-3 VWD. Inexpensive desmopressin was effective in those who responded well. Local hemostatic measures and antifibrinolytic treatment were performed systematically.

Adolescent↗

PubMed2002

Effects of an enhanced heart rate reserve on aerobic performance in patients with a heart transplant.

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.

Adrenergic alpha-Agonists↗

PubMed2002

Fuel oxidation during exercise in middle-aged men: role of training and glucose disposal.

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.

Blood Glucose↗

PubMed2002

Effect of training on the GH/IGF-I axis during exercise in middle-aged men: relationship to glucose homeostasis.

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.

Adaptation, Physiological↗

PubMed2002

Effect of prolonged undernutrition on rat diaphragm mitochondrial respiration.

Previous studies have shown that undernutrition induces an impairment of the respiratory muscle function in patients with chronic lung disease. To explain this, we hypothesized that undernutrition could decrease oxidative metabolism in the diaphragm. We therefore examined the effect of prolonged undernutrition on diaphragm mitochondrial oxygen uptake with pyruvate and palmitate as substrates in adult rats. Ten rats served as controls (CTL). Ten nutritionally deprived rats (ND) received 40% of their estimated daily nutrition. Five weeks of undernutrition induced a 33% decrease in state 3 respiration with pyruvate plus malate as substrate (993 +/- 171 versus 1488 +/- 167 nmol atomic O/mg/min, P < 0.01) and a 39% decrease with palmitate plus malate (516 +/- 89 versus 850 +/- 165 nmol atomic O/mg/min, P < 0.05). With succinate plus rotenone, there was no significant difference in the respiratory rate between groups. In the ND group, we found a significant decrease in citrate synthase activity (P < 0.01), and also in reduced nicotinamine adenine dinucleotide (NADH) dehydrogenase activity (P < 0.05), which cannot alone induce such a state 3 respiratory decrease. This showed that undernutrition in rat diaphragm does not induce an alteration in protein complexes I, II, III, and IV, or the F complex containing the mitochondrial ATPase of the electron transport chain. In conclusion, the main result of this study was that prolonged undernutrition induced a decrease in mitochondrial respiration secondary to a significant reduction in NADH generation by the Krebs cycle, which may affect respiratory muscle function with implications for patient care.

Animal Nutritional Physiological Phenomena↗

PubMed2002

Does haemorheology explain the paradox of hypoxemia during exercise in elite athletes or thoroughbred horses?

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.

Animals↗