Emmanuelle Varlet-Marie

New fundamental and applied mechanisms in exercise hemorheology

The present article summarizes recent data presented at the Exercise and Hemorheology symposium during the 15th Conference of the European Society for Clinical Hemorheology and Microcirculation (June 28-July 1, Pontresina, Switzerland, 2009). The review starts with several unresolved paradoxes in exercise hemorheology. Then, we focus on the potential hemorheological and immunological mechanisms involved in the adverse events sometimes reported in exercising sickle cell trait carriers, and the role of habitual physical activity. In a fourth part, new results on the effects of acute hypoxia on blood rheology are presented. Finally, we will discuss recent experimental evidences on the role of exercise on the regulation of nitric oxide synthesizing mechanisms in red blood cell.

Both overall adiposity and abdominal adiposity increase blood viscosity by separate mechanisms.

While recent studies suggested that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio (WHR) in addition to body index mass (BMI) in assessing the risk of death, this issue remains cintroversial since most authors conclude that BMI explains almost all the obesity-related risk of diabetes and conary heart disease (CHD). We investigated the separate effects of BMI and WHR on blood rheology in 430 patients attending to a metabolic check-up and exhibiting all the spectrum of age (11-77 yr) and BMI (15-50 kg/m2). BMI and WHR are correlated to each other (r = 0.269; p = 0.009) and are both predictors of blood viscosity (BMI: r = 0.15516; p = 0.004; WHR: r = 0.3638; p = 0.03). However while looking at determinants of viscosity these correlations had not the same meaning. For BMI it was explained by its correlation with plasma viscosity (r = 0.17718; p = 0.00105) and red blood cells (RBC) aggregation (all Myrenne and SEFAM indices with r ranging between 0.226 and 0.430) while these parameters were not correlated to WHR. By contrast WHR was strongly correlated with hematocrit (r = 0.524; p = 0.0003) which was not correlated with BMI. A forward stepwise regression selected WRH as a better predictor of blood viscosity, excluding BMI. Thus both BMI and WHR are associated with increased blood viscosity but these correlations reflect separate mechanisms. These data suggest that both overall adiposity and abdominal adiposity induce hyper viscosity, consistent with epidemiological studies linking the risk of CHD to abdominal adiposity and BMI.

Obesity-related increase in whole blood viscosity includes different profiles according to fat localization.

In a precedent study we observed that overall adiposity evaluated with the body mass index (BMI) was correlated with plasma viscosity and red blood cells (RBC) aggregation while abdominal obesity as assessed with the waist to hip ratio (WHR) was correlated with hematocrit. We investigated this issue in 129 women (age 15-65 years, BMI: 15 to 44 kg/m(2), WHR: 0.65 to 1.13, fatness: 12-58%) who were divided into fatness groups: 17 underweight women (BMI <18.5), 75 normal weigh (BMI 18.5-24.9), 11 overweight (BMI 25-29.9), and 26 obese (BMI >30) divided according to WHR into 13 lower body and 13 upper body obese women. Whole blood viscosity significantly increases across obesity classes, and is higher in upper body than in lower body obesity (2.84 ± 0.08 vs 3.29 ± 0.09 mPa.s, p < 0.05). The correlations between whole blood viscosity and BMI (r = 0.383 p < 0.01) and WHR (r = 0.364 p < 0.01) are found again. The former is explained by correlations of BMI with plasma viscosity (r = 0.303 p < 0.01) and red cell rigidity (r = 0.356 p < 0.01) and the latter is only explained by a correlation between WHR and hematocrit (r = 0.524 p < 0.01). BMI is also correlated with RBC aggregation parameters. Actually, when total fatness is evaluated with the percentage of fat (%fat) given by bioimpedance analysis (BIA), the picture is slightly different, since %fat is correlated with whole blood viscosity and RBC aggregation parameters but not with hematocrit, plasma viscosity and red cell rigidity. Fat free mass is also correlated with whole blood viscosity (r = 0.227 p < 0.02) due to a correlation with hematocrit (r = 0.483 p < 0.01) but neither RBC rheology nor plasma viscosity. This study shows that fatness by its own is associated with increased red cell aggregation, that abdominal fat increases blood viscosity due to a rise in hematocrit, and that overall body size as assessed with the BMI is associated with increased plasma viscosity and red cell rigidity.

Relationships between insulin sensitivity measured with the oral minimal model and blood rheology.

In studies using the intravenous glucose tolerance test with minimal model analysis we reported that low insulin sensitivity (SI) is associated with increased erythrocyte aggregability and plasma viscosity, that appeared to be markers of insulin resistance. Recently, development of modelling has made available a new approach of insulin sensitivity from oral glucose tolerance test data (oral minimal model). We aimed at determining in 111 subjects (51 men, 62 women, age 11-77 yr), insulin sensitivity with this approach together with blood viscosity parameters. With this approach the Myrenne indexes of red cell aggregation were negatively correlated to SI (M; r = -0.456; p = 0.0007; M1; r = -0.397; p = 0.004) while plasma viscosity was not. Correlations with fasting insulin levels (Ib) were weaker (M; r = 0.2711; p = 0.05; M1; r = 0.373; p = 0.007). Accordingly, a stepwise regression analysis selects M as the best correlate of SI and M1 as the best correlate of Ib. With this approach plasma viscosity does not exhibit any clear relationship with SI. This study supports the concept that RBC hyperaggregability is the prominent hemorheologic symptom of insulin resistance.

Measurement and Physiological Relevance of the Maximal Lipid Oxidation Rate During Exercise (LIPOXmax)

Jean-Frederic Brun1, Emmanuelle Varlet-Marie2, Ahmed Jerome Romain3 and Jacques Mercier1 1U1046, INSERM, Universite de Montpellier 1, Universite de Montpellier 2, Montpellier, CHRU Montpellier, Departement de Physiologie Clinique, Montpellier, 2Laboratoire Performance Sante Altitude, Sciences et Techniques des Activites Physiques et Sportives, Universite de Perpignan Via Domitia, 3Laboratoire EA4556 Epsylon, Dynamique des Capacites Humaines et des Conduites de Sante (Montpellier) France

Blood rheology and body composition as determinants of exercise performance in female rugby players

Athletes involved in rugby are characterized by a very specific pattern of body composition with an unusually important muscle mass. In a preceding study about rugbymen we evidenced that they exhibit a correlation between red blood cell aggregability and the amount of body fat although it remains within a normal range, and that red cell rigidity was correlated to isometric adductor strength. We had the opportunity of studying the relationships among exercise performance, body composition and hemorheology in 19 female rugby players (age 19-26, mean: 24.47 ± 0.67 yr) practising 4 - 10 hr/wk (mean 7.15 ± 0.3) since 1-12 yr (mean 4,05 ± 0,694). VO2max was not related by its own to blood rheology, either hematocrit (r = -0.0717 p = 0.7706) or plasma viscosity (r = 0.0144; p = 0.9533), but other markers of performance exhivited a correlation with red cell rheology. Relationships between fitness and body composition were evidenced. Isometric handgrip strength was negatively correlated to red blood cell aggregability (Myrenne M, r = -0.57839; p = 0.00948 M1 r = -0.58910; p = 0.00795). Adductor isometric strength was negatively correlated to red blood cell aggregability Myrenne M (r = -0.5033; p = 0.0280) but not to M1 (r = -0.4227; p = 0.0714). Fat mass is a major determinant of the maximal oxygen consumption VO2max either measured by a field test (r = -0.766; p = 0.00013) or exercise test (r = -0.575; p = 0.00994) and was also negatively correlated to both handgrip (r = -0.4918; p = 0.0325) and RBC aggregability M (r = -0.57839; p = 0.00948 and M1 r = -0.5891; p = 0.00795). Independently of fat mass, FFM appears to be a determinant of blood viscosity (r = 0.4622; p = 0.0463) due to its correlation with RBC rigidity (r = 0.4781; p = 0.0384). Thus, trained young women exercising 4-10 hr/wk and thus exhibiting a low percentage of body fat exhibit clear relationships between body composition and hemorheology, but fat mass being low, the parameter correlated with blood rheology is in this case fat-free mass, consistent with recent findings indicating that high fat mass in women is sometimes correlated with parameters of the metabolic syndrome such as insulin resistance or inflammation. In addition, parameters quantifying fatness even within such a physiological range are in this sample negatively related with exercise performance.

Are overall adiposity and abdominal adiposity separate or redundant determinants of blood viscosity

In line with recent literature showing that both general adiposity and abdominal adiposity are independently associated with the risk of death, we recently reported that body mass index (BMI) and waist-to hip ratio (WHR) were independent predictors of blood viscosity, related to different determinants of viscosity (for BMI: plasma viscosity and red cell aggregation; for WHR: hematocrit). Since this report was challenged by a study showing that abdominal adiposity (as measured with waist circumference WC and not WHR) is the only independent determinant of viscosity, we re-assessed on our previous database correlations among viscosity factors, BMI, WHR and WC. Blood viscosity was correlated to BMI (r = 0.155 p = 0.004), WHR (r = 0.364; p = 0.027) and WC (r = 0.094; p = 0.05). Hematocrit was correlated to WHR (r = 0.524) but neither to BMI (r =-0.021) nor waist circumference (r = 0.053). WC was correlated with plasma viscosity (r = 0.154; p = 0.002) while WHR was not (r =-0.0102 NS). A stepwise regression analysis selected two determinants of whole blood viscosity at high shear rate: BMI (p = 0.0167) and WC (p = 0.0003) excluding WHR. Therefore, in this sample, abdominal fatness expressed by WC and whole body adiposity remain independent determinants of blood viscosity. WHR and WC have not the same meaning, WC measuring the size of abdominal fat while WHR measuring the shape of body distribution regardless the degree of fat excess. Interestingly, hematocrit is rather related to shape (even within a normal range of body size) than the extent of abdominal fatness, and is not related to whole body adiposity.

Nutritional and metabolic determinants of blood rheology differ between trained and sedentary individuals

Body composition and nutrition have been reported to be correlated with blood rheology. However, in sedentary and in physically active individuals these relationships seem to be not exactly similar. This study investigated whether exercise training status influences these relationships. 32 athletes (ATH) (age: 25 ± 0.7 yr; body mass index (BMI): 23.75 ± 0.23 kg/m2) were compared to 21 sedentary subjects (SED) (age: 45.19 ± 2.90; BMI = 33.41 ± 1.33) with nutritional assessment (autoquestionnaire), bioelectrical impedancemetry, viscometry at high shear rate (MT90) and Myrenne aggregometer. Subjects differ according to age, weight and adiposity parameters. Their eating behavior is different: ATH eat a higher percentage of protein (p < 0.005), a lower percentage of lipid (p < 0.05), and a higher total amount of carbohydrate (+31% p < 0.02). Their viscosity factors are similar except plasma viscosity which is higher in SED than ATH (1.51 ± 0.03 vs 1.43 ± 0.02 mPa.s, p < 0.05). In both ATH and SED, abdominal obesity (waist-to-hip ratio or WHR) is associated with impairments in blood rheology, but not exactly the same. In ATH, WHR is associated with an increase in hematocrit (r = 0.647; p = 0.009), plasma viscosity (r = 0.723; p = 0.002), and caloric (and CHO) intake moderately increase RBC rigidity (r = 0.5405; p = 0.0251) and aggregability (r = 0.3366 p = 0.0596). In SED the picture is different, adiposity increases hematocrit (r = 0.460; p = 0.048), abdominal fatness increases blood viscosity independent of hematocrit, and CHO intake is associated with lower RBC aggregability (r = -0.493; p = 0.0319).

Hematocrit and hematocrit viscosity ratio during exercise in athletes: Even closer to predicted optimal values?

The hemorheological theory of optimal hematocrit suggests that the best value of hematocrit (hct) should be that which results in the highest value of the hematocrit/viscosity (h/η) ratio. Trained athletes compared to sedentary subjects have a lower hct, but a higher h/η, and endurance training reduces the discrepancy between the actual hct and the ⪡ideal⪢ hct that can be predicted with a theoretical curve of h/η vs hct constructed with Quemadas model. In this study we investigated what becomes this homeostasis of h/η and hct during acute exercise in 19 athletes performing a 25 min exercise test. VO2max is negatively correlated to resting hct and positively correlated to discrepancy between actual and ideal resting hct which is correlated to the maximal rise in hct during exercise. Predicted and actual values of the h/η were fairly correlated (r = 0.970 p < 0.001) but the actual value was lower at rest and this discrepancy vanished at 25 min exercise. Exercise-induced decrease in discrepancy between actual and theoretical h/η was negatively correlated with the score of overtraining. All these findings suggest that h/η is a regulated parameter and that its model-predicted ⪡optimal⪢ values yield a ⪡theoretical optimal⪢ hct which is close to the actual value and even closer when athletes are well trained. In addition, acute exercise sets h/η closer from its predicted ideal value and this adaptation is impaired when athletes quote elevated scores on the overtraining questionnaire.