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J Appl Physiol 98: 1258-1263, 2005. First published November 12, 2004; doi:10.1152/japplphysiol.00991.2004
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Inter- and intrastrain variation in mouse critical running speed

Veronique L. Billat,1 Etienne Mouisel,1,2 Natacha Roblot,2 and Judith Melki2

1Unité de Formation et de Recherche Fondamentale et Appliquée, Laboratory of Exercise Physiology EA3872, and 2Molecular Neurogenetics Laboratory, Institut National de la Santé et de la Recherche Médicale, E223, University of Evry, Evry, France

Submitted 9 September 2004 ; accepted in final form 5 November 2004


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
With the generation of mouse models of human cardiovascular or neuromuscular disorders, the development of noninvasive methods to evaluate the physiological responses to exercise presents an important challenge. The possibility for determining critical speed (CS) in the mouse model was examined according to strain (CD1, C57BL/6J, FVB/N) and sex. Sixty mice performed four exhaustive runs on a treadmill to determine their CS. Twenty-one performed an incremental test to determine the velocity at the lactate threshold. CS was significantly different between the strains (P < 0.0001) but not between sexes. Two measures of heritability showed that CS was partially heritable. CS was not significantly different from lactate threshold velocity. We conclude that CS, which reflects the aerobic capacity, can be determined in mice, as in humans and horses. Considering the intrastrain variability, CS could represent a valuable means for designing an optimal and individualized physical training in mice.

heritability; exercise

EXERCISE PROVIDES ONE OF THE most severe, yet physiological stresses to the cardiovascular system and represents a major determinant of the utilization of metabolic substrates. The adaptations to exercise are the result of a coordinated response of multiple organ systems, including cardiovascular, pulmonary, endocrine-metabolic, immunological, and skeletal muscle. With the generation of mouse models of human cardiovascular or neuromuscular diseases, the development of noninvasive methods represents an important goal toward an accurate evaluation of physiological responses to stress (5).

In the present study, we investigated the possibility that critical speed (CS), a well-recognized parameter of motor performance in humans (32) and more recently in horses (26), could be used to assess the aerobic capacity in mice. CS is based on the hyperbolic relationship between speed and time to fatigue for individuals during separate bouts of exhaustive runs performed at different speeds (35). Therefore, the tolerable duration of high-intensity exercise decreases hyperbolically as a function of the speed. The CS is the y-axis asymptote of this relationship and can be sustained theoretically to infinity but experimentally between 40 and 60 min. This hyperbolic relationship between speed and time to exhaustion can be transformed to a linear relationship between distance run and time to fatigue, according to the following equation linking the time to cover a distance (d) (10, 32): d = ADC + CS x t, where t is the time to exhaustion (in seconds) at a given speed, CS is in meters per second, and ADC is the so-called anaerobic distance capacity, i.e., a finite quantity of distance (meters) that can be covered above the CS by using energy derived from anaerobic glycolysis, phosphate, and oxygen stores. Therefore, CS and ADC are representative of the aerobic and anaerobic metabolisms, respectively (10, 32). Furthermore, the CS has been shown to be the highest constant work rate that can be sustained without inexorably increasing O2 uptake (O2), blood lactate, and H+ (33). Genetic traits contribute to the aerobic phenotype and to the adaptation to exercise (6, 7). In addition, given the tight relationship between genetic and environmental factors in the aerobic capacity, studying animal models carrying genetic modifications and submitted to minimal environmental variations could be of substantial value for identifying the genetic components of aerobic capacity variability (8). The CS determination does not require any invasive material and could represent a valuable means for measuring motor performance enhancement after a training protocol or a medical treatment in animal models.

The main purpose of this prospective study was to explore the possibility of using the CS concept in a mouse model and to evaluate inter- and intrastrain variability of CS, as well as a sex effect. Therefore, this study examined two hypotheses: 1) that critical running speed can be used as an indicator of exercise performance, and 2) that different inbred mouse strains differ in critical running speed after we checked the sex effect in one strain (the C57 BL/6J).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Animals.   Four groups of 15 mice were tested: 3 groups of males of different strains, CD1, FVB/N and C57BL/6J, and one group of females of the C57BL/6J genetic background. Among each group, seven mice performed the incremental test to determine the speed at the lactate threshold [lactate threshold velocity (vLT)]. All mice were purchased from Charles River (Charles River Laboratories, L'Arbresle, France). Mice were maintained in our animal house in pathogen-free environment, at 22°C with 12:12-h light-dark cycles, and had water and food ad libitum (A03–10, SAFE, Villemoisson-sur-orge, France). Mice were included into the training protocol at 8 wk of age. Fifteen males maintained on FVB/N, CD1, and C57BL/6J genetic backgrounds and fifteen C57BL/6J females were analyzed. FVB/N and CD1 were selected according to their high-performance level in endurance exercises on the treadmill or wheel (27). C57BL/6J was chosen because it is the most commonly used strain for genetic and/or transgenic study. All animal procedures used in this study were performed in accordance with institutional guidelines (agreement numbers A91–228-2 and 3429).

Evaluation of the CS.   Mice were maintained in our animal house for 1 mo before being included into the training protocol. The mice ran on a 10.6 x 30-cm double-lane treadmill (LE 8709, Bioseb, Chaville, France). A shock grid that delivered 0.2 mA was placed 10 cm from the rear of the cell to provide a stimulus to make the animals run (28, 38). The protocol consisted of four runs leading to exhaustion, according to previous studies (9, 10). A single trial was performed per day, and the protocol covered a period of 4 days. Each trial consisted of a run at constant speed. Four speeds were tested in each mouse (18–51 m/min). The time that the mice were able to run was recorded at each speed and was arbitrarily limited to 45 min or exhaustion, as defined by a total number of 50 shocks. Two parameters were used to estimate endurance performance: the distance (in meters) the mice were able to cover at a given speed and the time to cover the distance (limit time, seconds). The CS and ADC were calculated, respectively, from the slope (a) and the intercept (b) of the regression line, plotting the distance vs. the time to exhaustion from the four tests, according to the equation y = ax + b (Fig. 1).



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  		Fig. 1. Determination of critical speed (CS) in one mouse (CD1) on the treadmill, according to the protocol described in MATERIALS AND METHODS.

 
Incremental exercise test.   This second test was performed to determine the lactate threshold. Three days after the evaluation of CS, mice performed an incremental test consisting of a starting speed of 70% of their CS for 3 min. Then a 5% increased speed was applied every 3 min to reach a final speed of 120% of CS for 3 min. Each step was separated by a 20-s rest. Blood lactate concentration was determined in a sample (5 µl) collected from the tip of the tail using a lactate pro-LT device (Arkray, Kyoto, Japan). Blood was collected before the onset of incremental test, during rest, and 2 min after the end of exercise. The vLT was defined as the speed at which an increase of >1 mM occurred when lactate concentration was between 3.5 and 5 mmol/l. In humans, this range method of vLT determination has previously been reported to estimate the maximal lactate steady state in an incremental exercise protocol (1). Furthermore, in humans and also in rats, it has been shown that the maximal blood lactate concentration compatible with a lactate steady state was, in most of the subjects and exercises, between 3 and 6 mM (1, 3, 4). Furthermore, given that, for most data collected, a decrease in blood lactate was observed after the first increase, vLT was determined when blood lactate criteria were observed without any further increase in blood lactate concentration (Fig. 2).



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  		Fig. 2. Determination of velocity at the lactate threshold (vLT) in one mouse (C57BL/6J male) on the treadmill, according to the protocol described in MATERIALS AND METHODS. In this mouse, vLT is at 95% of the CS. [La], lactate concentration; CV, coefficient of variation.

 
Statistical analysis.   The strain and sex effect on the CS was tested in all mice (15 in each group), whereas the comparison between the CS and the lactate threshold speeds was carried out on seven mice in each group. Tests for statistically significant differences between strains or sexes were performed, based on the assumption of the normality and of the equality of the variance, using Sigmastat 2.03 software (SPSS). A one-way analysis of variance was performed to test the strain effect. If analysis of variance indicated significant differences, post hoc Dunnett's t-test was applied to evaluate intrastrain differences (2). For each parameter, the strain displaying the lowest average value was compared with other strains to determine which strain differed significantly from the lowest. Differences between sexes were evaluated in C57BL/6J genetic background using Student's t-test for nonpaired data (n = 7). Correlations between lactate threshold and CS on one side and between CS and ADC on the other side were evaluated using the Pearson correlation test. Results are presented as means ± SD.Statistical significance was set at P < 0.05.

Determination of heritability of the CS, lactate threshold speeds, and anaerobic capacity was calculated by estimating broad-sense heritability. Broad-sense heritability is usually considered as the degree to which the phenotype is determined by the genotype (13). Interclass correlations and the coefficient of genetic determination (g2), two measures of heritability in the broad sense, were calculated using methods outlined by Festing (15) and Falconer and Mackay (13) and recently applied by Lightfoot et al. (28) to estimate the interstrain variation in murine aerobic capacity. Intraclass correlations (rI) were defined as the proportion of the total variation that was accounted for by genetic differences between the strains, whereas the calculation of the g2 provided a similar indication but corrects for the doubling of genetic variance that occurs with inbreeding (15). The rI and g2 were calculated as follows: rI = (MSB – MSW)/[MSB + (n – 1)MSW] and g2 = (MSB – MSW)/[MSB + (2n – 1)MSW], where MSW and MSB are the within- and between-strain mean square, respectively, i.e., the mean square of the within- and between-strain comparison, and n is the number of animals per strain (15, 27, 28).


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Validation of critical running speed in mice.   CS was determined in 60 mice belonging to FVB/N, CD1, and C57BL/6J strains. The coefficient of determination (r2) of the distance-time running relationship was >0.98, whatever the strain and the sex (Table 1). As in humans and horses, the CS model is reliable in mice, as the distance-time-to-exhaustion relationship follows a regression line not significantly different from zero. To determine whether CS could be used to evaluate inter- or intravariation, this physiological parameter was evaluated in three different genetic backgrounds using the same protocol. Statistically significant lower CS was observed in C57BL/6J mice (18.0 m/min) compared with either FVB/N (22.0 m/min) or CD1 (24.1 m/min, P < 0.0001, Table 1) (Fig. 3). The CS of the FVB/N and CD1 mice was not significantly different (P = 0.15, n = 15). However, the ADC was not significantly different between strains (P = 0.30). This could be due to the high variability of anaerobic distance within strain. Indeed, ADC coefficient of variation was 63, 39, and 32% for the CD1, FVB/N, and C57/BL6J, respectively. Regarding CS, the intravariability equaled 9, 19, and 10% for the CD1, FVB/N, and C57/BL6J, respectively.


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  		Table 1. Critical speed, anaerobic distance capacity, and determination coefficient of the relationship between distance run and time to fatigue according to strain and sex of the mice

 


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  		Fig. 3. The distance-time and CS (the slope of the regression line) in the 3 strains.

 
In contrast to the strain effect, there was no sex effect on CS, ADC, and the determination coefficient of the distance run-time to fatigue relationship in the C57/BL6J. This strain was the only one investigated for estimating the sex effect (Table 1). Two measures of heritability of the CS, i.e., the rI and the g2, were both significant for CS (0.45 and 0.30, respectively) but not for ADC (0.010 and 0.011, respectively).

The critical vs. the lactate threshold speed.   The CS was also not significantly different from the lactate threshold speed in all mice (Table 2). Considering all of the mice (n = 60), >70% of the variance of the lactate threshold speed could be estimated by the CS (Fig. 4).Blood lactate concentration at and above the lactate threshold was significantly higher in the FVB/N mice compared with C57BL/6J and CD1 (Fig. 5). In contrast, for the C57/BL6J, there was no significant difference in blood concentration below, at, and above the lactate threshold between sexes (blood lactate concentration at the lactate threshold was 3.8 ± 0.7 vs. 4.3 ± 0.4 mM for males and females, respectively, P = 0.11) (Fig. 5). These data indicate that CS could be determined in mouse with tight correlation to vLT, a feature similar to that found in humans (9, 11).


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  		Table 2. Lactate threshold speed and critical speed of the mice according to their strain and sex (among the C57/BL6J)

 


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  		Fig. 4. Relationship between the CS and the vLT (n = 28). More than 70% of the vLT variance can be predicted by the variance of the CS.

 


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  		Fig. 5. Strain and sex (for the C57BL/6J) effect on the blood [La] running at speeds below, at, and above the vLT. The speeds are expressed as a percentage of the CS. Values are means ± SD. Open, shaded, and solid bars show the average blood [La] at run speeds below, at, and above the vLT, respectively. §Significantly different from the C57BL/6J; {ddagger}significantly different from the FVB: P < 0.05.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
This study describes a procedure for the noninvasive measurement of exercise capacity in mice using critical running speed as an approximation of lactate threshold for estimating the aerobic capacity in humans, horses, rats, or mice (4). To our knowledge, this is the first study demonstrating that the model of CS can be applied in mice. The critical running speed is not different between sexes for the C57BL/6J, the strain on which this factor was tested. However, the CS differed significantly between the strains, with the C57BL/6J and the CD1 being the slowest and fastest strain, respectively. However, the intragroup variability of the CS showed that training speed and duration must be individualized even within strain and sex. Given the fact that mice represent an excellent genetic model underlying exercise performance, this approach could provide a valuable and easy-to-use tool for such studies.

The model of CS for the estimation of the aerobic capacity in mice.   The CS model can effectively be applied in mice running on a treadmill. This study showed very high r2 values (>0.98) when the simple polynomial expression (y = ax + b) was used to determine CS from four tests. This value of r2 was above those reported in some human studies (9, 10, 32). A true linear relationship was found (and then r2 close to 1) when CS is calculated with at least four trials, lasting between 1 min 30 s and 20 min (9). We found that, in mice, this protocol should be followed to avoid CS variability. The protocol of four trials performed in 1 wk was compatible with the recovery ability of the mice.

Taking into account these recommendations, we observed a moderate coefficient of variation in each group (<10%), except for the FVB/N. However, we can consider that this variability is nonnegligible in a group of animals having the same genetic background and environment. Part of this variability can be explained by the aerobic characteristics of the individual but is also probably related to some training problem. Indeed, some of the variability might be due to some of the animals' experienced training to the treadmill run until exhaustion. Therefore, we observed that some C57BL/6J mice reached the maximal number of shocks without being exhausted, suggesting that the conditioning was not efficient. Therefore, the time that the mice were able to maintain the intermediate speed did not increase as much as expected by their time to exhaustion at higher speed. Such a problem did not occur with CD1 mice. All CD1 displayed a high ability for running on the treadmill. Nevertheless, the variability of the CS in the CD1 was only slightly less (8.9%) than that of C57BL/6J (10.2%).

These data indicate that an individual calibration of intensity and duration of training should be necessary, even in mice belonging to the same strain. Furthermore, the measurement of CS as an assessment of the aerobic capacity and a means for training calibration in mice could offer an alternative to the usual incremental exercise, which measured the total endurance time. On the treadmill, performance model and aerobic capacity in mice are generally assessed by total exercise time during an incremental speed or grade (12, 28). In the incremental test, the performance depends on the highest speed reached by the animal, even for a short time. The first speed stage of these standard incremental tests was the same whatever the strain (19.8 m/min) (27). Therefore, this protocol did not take into account the interstrain variability. Indeed, the speed (19.8 m/min) represents 78, 87, or 120% of the CS of the CD1, FVB/N, and C57BL/6J found in our study, respectively. In the same manner, the standard speed increments (1.5 m/min) generally used in mouse exercise protocol also represent a different relative speed (5–10%) of the CS, according to strain. Exercise duration at a given speed has also been used to estimate aerobic endurance capacity in mice (11). However, the calculation of the CS from four trials allows a more accurate evaluation of aerobic capacity than when based on a single trial (3, 4).

This coefficient of variation is similar to that observed in healthy and untrained humans (14) but much higher than in studies performed in well-trained endurance subjects (8, 9). The mice studied here were untrained, and the animals had no wheel in their cages to allow spontaneous training, which is reported to be efficient for improving aerobic capacity (19, 21, 38).

The determination of the CS could provide a reference for better estimating the exercise input in mice, and CS could indeed be more consistent in further studies in the assessments of the effects (especially at a molecular level in animals) of training. Indeed, the nature of fatigue (i.e., failure to sustain a required power output) and training response will be influenced by the type of exercise, its intensity, and duration (10). In humans, it has been clearly shown that the CS delineates the so-called "severe-intensity" domain (33) at which no gas exchange or metabolic steady state can be achieved. Rather, blood lactate, lactate-to-pyruvate ratio, and H+ concentration continue to rise (presumably reflecting intramuscular changes); bicarbonate falls; and O2 rises inexorably toward maximum O2 (O2 max) (3, 4, 33). The CS is close to the lactate threshold evaluated by determining blood lactate concentration by using incremental, multistage treadmill exercise test to determine the speed at the lactate threshold (3, 4, 9). We chose, in the present study, this procedure, which has previously been validated in horses (24, 43) and in rats (25, 42).

According to the reference values of O2 max in mice (150–170 ml·kg–1·min–1) and their energy cost of running (14, 36, 45), we can estimate that the CS in our untrained mice elicits ~75% of O2 max. This figure is in accordance with the lack of significant difference between the critical and the lactate threshold speed, as previously reported in humans (9). These results would offer a potential application of the mechanisms for controlling exercise metabolism, as it has been recently reported that mice mimic human responses to exercise after an intensive interval training performed at 85–90% of O2 max (22, 45), which is the intensity range of the CS in humans (3, 4). Indeed, the adaptive response in the fast-twitch white fibers began at 80% O2 max and increased exponentially when intensity was increased. Therefore, CS could be a reference if the target is to enhance the oxidative capacity of the type II fibers. Indeed, the work rate associated with the lactate threshold speed is considered as being an indicator of endurance exercise capacity in humans and horses (24, 43) and in rats (25, 42).

The lactate threshold speed has been reported to be sensitive to endurance training (3, 4, 43). Furthermore, the time to exhaustion at the lactate threshold speed has recently been reported to increase by 50% after training when O2 max and maximal lactate steady-state workload increased by only 5% for O2 max (3). Therefore, the CS, which takes into account the time to exhaustion in a range of speeds between 70 and 120% of O2 max, has been reported in humans to be more sensitive to training than the maximal O2 or the speed at the lactate threshold (44).

If the CS represents the aerobic capacity, ADC provides an estimation of the energy to run faster than CS during a finite time. This has been used in humans (10, 33) and in horses (26) to estimate the anaerobic work capacity without the need for measuring the oxygen deficit, which is materially much more difficult, especially in horses. This ADC has, however, a great variability within mice of the same strain (30–40%). This is rather surprising as the mouse is an animal that has a naturally high percentage of fast fiber type, and we expected a more homogeneous anaerobic work capacity. Therefore, if the measurement of the CS was satisfactory, the ADC associated with this model (i.e., the intercept on the y-axis) should be an artifact of the slope (i.e., the CS) and should be interpreted with caution and compared with the oxygen deficit measurement (3, 4). The difference in performance between mice belonging to the same strain could be attributed as much to the anaerobic capacity as the aerobic capacity. ADC was between 35 and 46 m, according to the strain, but with a very high intragroup variability. These results indicate that ADC was not a reliable criterion to assess the anaerobic capacity, ADC, as previously reported in humans or horses. Oxygen deficit should represent a more valuable tool to evaluate the anaerobic metabolism. Further studies are, however, required to explore the possible relationship between the oxygen deficit assessing the anaerobic work capacity and the ADC in mice (10, 30).

The CS variability in mice according to the strain and the sex.   The CS reflects the aerobic capacity, which is a complex trait determined by the multifactorial interplay between genetic and environmental factors. It is widely accepted that an individual's traits depend on both genetic background and environmental factors (31). Given the complexity, the creation of animal models in which both genetic and environmental variations approach minimums can be of substantial value (41). The laboratory mouse model allows an investigation on how the genetic influences phenotypic differences, such as the training responsiveness (40). Up to now, the molecular mechanisms of adaptative cardiac and muscle modification in response to physiological stimuli remain virtually unexplored because of a paucity of effective and well-controlled experimental models in this species. The only study using intensity controlled treadmill running in mice instead of the voluntary exercise regimen with little control of exercise intensity, and the individual's fitness level has recently been performed in mice C57BL/6J of both sexes (22). This study was very effective in the improvement of ventricular weight, O2 max, running economy (i.e., the energy spent by unit of body mass and meter run), and skeletal muscle mass (22). The individualized intensity training for mice is promising, but, in this previous study, the training intensity was calibrated in reference to O2 max, which requires a rather sophisticated and expensive protocol.

The present study addressed the possibility of determining a CS for mice running on a treadmill in a perspective of aerobic capacity assessment and of exercise intensity reference. For that, we checked that the CS had a greater significant difference between than within strains. We chose to compare the C57BL/6J, widely used as a biomedical model (27, 40), with the other two strains, the FVB/N and CD1 chosen for their high ability to run (27). The CS of the C57BL/6J was significantly lower than those of the CD1 and FVB/N. This is in accordance with the study by Lerman et al. (27), which showed that C57BL/6J demonstrated the lowest maximum speed of all six other strains determined in an incremental speed protocol (22.2 vs. 40.8 m/min for the FVB/N strain, which was the fastest). Logically, the C57BL/6J demonstrated a significantly greater number of beam breaks per minute during a 30-min treadmill run at 19.8 m/min compared with all of the other strains, whereas the CD1 and FVB/N had the lowest number (27). This method for measuring the endurance of the mice did not take into account the fact that the mice did not run at the same percentage of their maximal speed (90% for the C57BL/6J vs. 48.5% for the FVB/N). In this study, the endurance test consisted of four independent trials for the CS determination. This endurance test was then maximal for all of the strains in the same conditions of stress (50 electric shocks). Therefore, this endurance test could be used to recalculate training exercise intensity with respect to the endurance and speed variability between and within strains. The CS integrates the speed and time duration difference between individuals and strains. However, the C57BL/6J consistently showed the highest level of voluntary wheel-running, not only for the duration (hours of running by night), but also by the average speed and the distance run. The second-best strain was the CD1, and far behind was the FVB/N. These authors concluded that an animal's performance under forced exercise conditions does not necessarily predict how that animal will perform in a voluntary setting. We have to add that the endurance test was not performed at the same relative exercise intensity, according to the strain, as discussed previously, and that the ergometer was not the same. A voluntary exercise model on a nonmotorized treadmill has not yet been reported.

Broad-sense heritability estimates for CS were rI = 0.45 and g2 = 0.30, which were of same order as the voluntary wheel-running duration performance and distance run (27, 38), maximal speed in horses (16, 17, 20, 34), and CS in horses (X. Quilliet and V. L. Billat unpublished observations). Furthermore, even if this exercise model is successfully used for selective breeding (21), this selection could be more based on the behavior than on endurance capacity (18, 29, 37, 39). We may suggest that the CS could also be a method of improving the effectiveness of selective breeding, with the purpose of improving aerobic capacity.

Conclusion.   The present study shows that it may be possible to determine, as in humans and horses, a CS, as the distance-time-to-exhaustion relationship follows a regression line not significantly different than zero. The CS is not significantly different from the blood lactate threshold speed at an intensity that was estimated to be 75% of O2 max, according to the standard value of running economy and O2 max reported in untrained mice by Kemi et al. (22). This does not change, whatever the strain and sex. Furthermore, the CS has a g2 of 0.40, which is similar to that obtained from a voluntary wheel-running test. We can suggest that the CS could be a means of selective breeding and training calibration to individualize the treadmill running intensity, even within a strain.

Therefore, the CS determination in mice of different strains could represent a relevant means of measuring the performance enhancement and of estimating modification of aerobic and anaerobic metabolisms, after a training protocol or medical treatment in mouse models. Because mice are an excellent genetic and transgenic model for studying the molecular biology and genetics of exercise performance and adaptation, this noninvasive approach has obvious value to the exercise research community.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported by grants from the Fondation d'Entreprise Gaz de France and Genopole to V. L. Billat and from Institut National de la Santé et de la Recherche Médicale, University of Evry, and the Fondation Bettancourt Schueller to J. Melki.


   FOOTNOTES
 

Address for reprint requests and other correspondence: V. L. Billat, Laboratory of Exercise Physiology, UFRSFA, Université d'Evry-Val d'Essonne Boulevard François Mitterrand, 94025 Evry Cedex France (E-mail: veronique.billat{at}wanadoo.fr)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

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