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Biomedical subjects

Corinne Caillaud

Publications and source records attributed to Corinne Caillaud.

12 recordsLinked to original sources

Does exercise-induced hypoxemia modify lactate influx into erythrocytes and hemorheological parameters in athletes?

This study investigated 1) red blood cells (RBC) rigidity and 2) lactate influxes into RBCs in endurance-trained athletes with and without exercise-induced hypoxemia (EIH). Nine EIH and six non-EIH subjects performed a submaximal steady-state exercise on a cyclo-ergometer at 60% of maximal aerobic power for 10 min, followed by 15 min at 85% of maximal aerobic power. At rest and at the end of exercise, arterialized blood was sampled for analysis of arterialized pressure in oxygen, and venous blood was drawn for analysis of plasma lactate concentrations and hemorheological parameters. Lactate influxes into RBCs were measured at three labeled [U-14C]lactate concentrations (1.6, 8.1, and 41 mM) on venous blood sampled at rest. The EIH subjects had higher maximal oxygen uptake than non-EIH (P < 0.05). Total lactate influx was significantly higher in RBCs from EIH compared with non-EIH subjects at 8.1 mM (1,498.1 +/- 87.8 vs. 1,035.9 +/- 114.8 nmol.ml(-1).min(-1); P < 0.05) and 41 mM (2,562.0 +/- 145.0 vs. 1,618.1 +/- 149.4 nmol.ml(-1).min(-1); P < 0.01). Monocarboxylate transporter-1-mediated lactate influx was also higher in EIH at 8.1 mM (P < 0.05) and 41 mM (P < 0.01). The drop in arterial oxygen partial pressure was negatively correlated with total lactate influx measured at 8.1 mM (r = -0.82, P < 0.05) and 41 mM (r = -0.84, P < 0.05) in the two groups together. Plasma lactate concentrations and hemorheological data were similar in the two groups at rest and at the end of exercise. The results showed higher monocarboxylate transporter-1-mediated lactate influx in the EIH subjects and suggested that EIH could modify lactate influx into erythrocyte. However, higher lactate influx in EIH subjects was not accompanied by an increase in RBC rigidity.

Adaptation, Physiological↗

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↗

Effect of age on Hsp72 expression in leukocytes of healthy active people.

Aging mammalians show reduced expression and induction of cytoprotective heat shock proteins in response to physiological stresses. Physical training can increase Hsp72 expression in young and old animals, but whether same adaptations can be observed in old people remains unknown. We hypothesized that the maintenance of physical activity during aging should preserve Hsp72 expression in leukocytes of elderly people. Intracellular and surface Hsp72 (the inducible form of Hsp70) expression in leukocytes as well as apoptotic and necrotic leukocytes were measured by flow cytometry at rest and after maximal incremental test on treadmill in the following groups: 8 young subjects (25.3+/-0.6 year, G25), 12 sexagenarians (66.2+/-1 year, G65) and 9 octogenarians (82.2+/-1.2 year, G85), all physically active. Protein and lipid oxidation markers were also measured at rest and post-exercise. Results showed significant lower basal percentages of Hsp72-positive lymphocytes in G85 compared to G25. At rest, lower mean fluorescence intensity in Hsp72-positive monocytes was measured in G65 and G85 compared to G25, and in granulocytes from G85 compared to G25. Maximal exercise test induced systemic oxidative-stress in the three groups but did not induce any increase in apoptotic or necrotic cells. We observed a significant increase in the percentage of Hsp72-positive lymphocytes from G85. This study showed that maintaining physical activity during aging can preserve the ability to induce Hsp72 in response to physiological stress.

Adult↗

Strengths and weaknesses of established indirect models to detect recombinant human erythropoietin abuse on blood samples collected 48-hr post administration.

We studied indirect detection models of erythropoietin abuse (EPO) on blood samples collected 48-hr after administration of the drug during 6 weeks of recombinant human erythropoietin (rHuEPO) treatment. Although the efficiency of OFF-models was preserved, we found a loss of sensitivity of ON-models. This study also revealed an increased percentage of stomatocytes in athletes receiving rHuEPO

Doping in Sports↗

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↗

Aerobic determinants of the decline in preferred walking speed in healthy, active 65- and 80-year-olds.

The preferred walking speed is a common measure of mobility that declines with age and has been related to maximal oxygen uptake (VO(2,max)). The present study determined whether this decline is associated with a higher percentage of the ventilatory threshold in older adults walking at their preferred speed. We compared the preferred walking speed and VO2 at this speed in relation to both VO(2,max) and VO2 corresponding to the ventilatory threshold (TVE) in healthy, physically active sexagenarians (G65, n=10) and octogenarians (G80, n=10) walking on a treadmill. The preferred walking speed was lower in G80 (1.16+/-0.09 m.s(-1)) than in G65 (1.38+/-0.09 m.s(-1); P<0.001). Energy expenditure and the energy cost of walking at the preferred walking speed were not significantly different between the two groups. G80 subjects exhibited significantly higher fractions of VO(2,max) (60.8+/-8.0%) and TVE (74.2+/-7.9%) at the preferred walking speed than G65 (42.9+/-5.0 and 53.2+/-5.7% respectively; P<0.001). Multiple regression analysis showed that the fraction of TVE was the main determinant, with a small contribution of height, in the decline in the preferred walking speed in healthy and active elderly subjects (R2=64%; P<0.001). These findings show that with age, walking at the preferred speed requires a higher fraction of TVE. This increase in the relative physiological effort at preferred walking speed could explain the reduction in this gait speed in healthy older subjects.

Aged↗

Faster oxygen uptake kinetics at the onset of submaximal cycling exercise following 4 weeks recombinant human erythropoietin (r-HuEPO) treatment.

We tested the hypothesis that prolonged administration of moderate doses of recombinant human erythropoietin (r-HuEPO) accelerates the initial rate of rise in pulmonary O2 uptake (VO2) in response to submaximal exercise and increases the maximal rate of O2 uptake (VO(2,max)). Sixteen endurance-trained athletes were divided into two groups: r-HuEPO- (n=9) or placebo-treated (n=7). r-HuEPO or placebo (saline) injections were given s.c. 3 times a week for 4 weeks. Exercise testing, before and after the 4 weeks, comprised incremental maximal tests and several transitions from rest to 10-min cycling exercise at 65% VO(2,max). VO2 was measured breath-by-breath during all tests. In the r-HuEPO group, resting haemoglobin concentration (+9.6%) and haematocrit (+8.3%), as well as VO(2,max) (+7.0%) and power output (+7.2%) increased significantly (P<0.05) after the 4 weeks, whereas no change was observed in the control group. The time constant of the primary VO2 response was significantly faster (+18%) after the 4 weeks r-HuEPO treatment than before (mean+/-SD; 29.3+/-4.5 vs. 35.7+/-7.4 s, respectively, P<0.05) but was unaffected in the placebo group (34.5+/-7.3 vs. 33.4+/-7.9 s). Collectively, our findings suggest that r-HuEPO contributes both to an acceleration of the dynamic response of VO2 to submaximal exercise and to an increase in maximal exercise capacity.

Adult↗

Energy cost of walking and gait instability in healthy 65- and 80-yr-olds.

This study tested whether the lower economy of walking in healthy elderly subjects is due to greater gait instability. We compared the energy cost of walking and gait instability (assessed by stride to stride changes in the stride time) in octogenarians (G80, n = 10), 65-yr-olds (G65, n = 10), and young controls (G25, n = 10) walking on a treadmill at six different speeds. The energy cost of walking was higher for G80 than for G25 across the different walking speeds (P < 0.05). Stride time variability at preferred walking speed was significantly greater in G80 (2.31 +/- 0.68%) and G65 (1.93 +/- 0.39%) compared with G25 (1.40 +/- 0.30%; P < 0.05). There was no significant correlation between gait instability and energy cost of walking at preferred walking speed. These findings demonstrated greater energy expenditure in healthy elderly subjects while walking and increased gait instability. However, no relationship was noted between these two variables. The increase in energy cost is probably multifactorial, and our results suggest that gait instability is probably not the main contributing factor in this population. We thus concluded that other mechanisms, such as the energy expenditure associated with walking movements and related to mechanical work, or neuromuscular factors, are more likely involved in the higher cost of walking in elderly people.

Adult↗

Strenuous exercise increases plasmatic and urinary leukotriene E4 in cyclists.

UNLABELLED: The purpose of this study was to investigate plasma and urinary levels of leukotriene (LT) and the changes in pulmonary function induced by strenuous exercise in highly trained cyclists (HT) with mild exercised-induced hypoxemia (EIH). METHOD: Nine HT and five untrained subjects (UT) performed a 30-min exercise at 78% of their VO2peak. Leukotriene E4 (LTE4) was assayed in plasma and urine. Pulmonary function tests and pulmonary diffusion capacity (DLCO) were examined before and after exercising. Ear arterialized blood gases were assessed at rest and during exercise. RESULTS: The mean drop in partial oxygen pressure was 15 mmHg in HT during exercise; and the DLCO decreased by 7.5% following exercise. No significant changes were found in forced vital capacity or forced expiratory flows. LTE4 levels increased significantly in HT following exercise: urinary LTE4 was 42.9 +/- 6.3 ng.mmol-1 creatinine at rest and 66.3 +/- 11.9 ng.mmol-1 creatinine 2 hrs after exercise, and plasma LTE4 rose from 528 +/- 91 pg.mL-1 at rest to 897 +/- 123 pg.mL-1 after exercise. By contrast, urinary LTE4 level was unchanged in the UT group. Among the HT group, there was no significant correlation between urinary LTE4 changes and PO2, air flow rates, or DLCO changes. CONCLUSION: These results suggest that strenuous exercise induces an increase of LTE4 release in highly trained cyclists with mild EIH. These changes in LTE4 levels were not related to significant impairment of lung function.

Adult↗

Exhaled nitric oxide level during and after heavy exercise in athletes with exercise-induced hypoxaemia.

Endogenous nitric oxide (NO) is an important mediator of vasodilatation, bronchodilatation and lung inflammation. We hypothesised that the exhaled NO level may be modified in some endurance-trained athletes during and after intense exercise. Nine athletes with exercise-induced hypoxaemia (EIH), 12 athletes without EIH and 10 untrained subjects exercised for 15 min at 90% maximal oxygen consumption (VO(2)max). Exhaled NO was measured during exercise, and after 1 h and 22 h of recovery. Exhaled NO concentration ( C(NO)) decreased significantly during exercise in all subjects and returned to basal values after 1 h of recovery with no further modification. Exhaled NO output (V(NO)) rose significantly during exercise, rapidly dropped down following exercise and was similar to resting values after 1 h and 22 h of recovery. The results also showed that C(NO) and V(NO) were significantly lower in the athletes with EIH in comparison with the untrained subjects (V(NO) was 5.32 +/- 0.77 nmol/min versus 3.61 +/- 0.72 nmol/min at rest, 18.52 +/- 1.50 nmol/min versus 15.00 +/- 2.06 nmol/min during heavy exercise, and 5.52 +/- 1.04 nmol/min versus 3.79 +/- 0.76 nmol/min after 22 h recovery, in untrained subjects and EIH athletes, respectively). These findings do not confirm the hypothesis of pulmonary inflammation associated with EIH. However, potential NO epithelial down-regulation may occur and contribute to the development of gas exchange abnormality in some endurance-trained athletes.

Adult↗

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↗

Beta2-agonists and exercise-induced asthma.

Beta2-agonists taken immediately before exercise provide significant protection against exercise- induced asthma (EIA) in most patients. However, when they are taken daily, there are some negative aspects regarding severity, control, and recovery from EIA. First, there is a significant minority (15-20%) of asthmatics whose EIA is not prevented by beta2-agonists, even when inhaled corticosteroids are used concomitantly. Second, with daily use, there is a decline in duration of the protective effect of long-acting beta2-agonists. Third, if breakthrough EIA occurs, recovery of lung function is slower in response to a beta2-agonist, and additional doses are often required to achieve pre-exercise values. If a person who takes a beta2-agonist daily experiences problems with exercise, then the physician should consider changing the treatment regimen to achieve better control of EIA. These problems likely result from desensitization of the beta2-receptor on the mast cell, which enhances mediator release, and on the bronchial smooth muscle, which enhances the bronchoconstrictor response and delays recovery from EIA. These effects are reversed within 72 h after cessation of a beta2-agonists. The important clinical question is: Are we actually compromising the beneficial effects of beta2-agonists on the prevention and recovery from EIA by prescribing them daily? Patients with EIA need to ensure that their doses of inhaled corticosteroid or other anti-inflammatory therapy are optimized so that, if necessary, a beta2-agonist can be used intermittently as prophylactic medication with greater confidence in the outcome.

Adrenergic beta-Agonists↗