Research Interests
Main research Interests Hemorheology and cell adhesion mechanisms in sickle cell trait (SCT) carriers during exercise Sicklecell disease (SCD) is caused by the mutation of hemoglobin (Hb) A into HbS and mainly affects people of African descent. This mutation is caused by the substitution of a single amino acid, valine for glutamic acid. SCD is marked by frequent episodes of painful vaso-occlusive crisis. Sickle cell trait (SCT) carriers are characterized by the heterozygous presence of both HbA and HbS (AS genotype) in their red blood cells (RBC).The prevalence of SCT is around 20-40% in some areas of Sub-Saharan Africa and reaches 15% in European metropolis. In normal physiological conditions, SCT is not associated with clinical symptoms. However, several studies have reported cases of health complications in SCT carriers when they were confronted to stressful physiologicalconditions such as hypoxia or strenuous exercise (Jones et al, 1970; Kark et al, 1987). The concept of benign condition for this population is therefore debated (Le Gallais et al, 2007; Connes et al, 2007; Baskurt et al, 2007; Bergeron, 2007; Boucher, 2008). We try to understand whether SCT carriers are characterized by abnormalities in blood rheological, inflammatory and coagulation responses during exercise in comparison with the normal population, that could be responsible for some of the sudden death cases reported in the litterature. Several parameters are investigated in our laboratory: 1) hemorheological parameters (blood and plasma viscosities, red blood cell deformability, red blood cell aggregation, red blood cell disaggregation shear rate threshold); 2) markers of inflammation and cell adhesion mechanisms (cytokines, molecules of the CAMs' and selectins' familly); 3) coagulation/fibrinolytic activity markers; 4) markers of oxidative stress. Indirect physiological markers of cardiovascular risk are also used, such as the analysis of heart rate variability that allow the determination of the activity of the autonomic nervous system (Connes et al, 2006). We recently demonstrated lower red blood cell deformability at rest and in response to exercise (particularly during the late recovery phase) in SCT carriers compared with control subjects (Connes et al, 2005; 2006; Tripette et al, 2007) that could increase the risk for microcirculatory complications. We recently test the hypothesis of oxidative stress involvement to explain the alterations in RBC deformability in SCT carriers and found no relation between RBC membrane lipid oxidation and RBC deformability alteration in this population. Specific kinetics of L- and P-selectins have also been observed in SCT carriers compared with a control population suggesting a shedding process that could be interpreted as a protective mechanism (Connes et al, 2008, Tripette et al, in press; Tripette et al, submitted). Very recent results from our group (Tripette et al, submitted) also support that RBCs from SCT carriers could be less easily dispersed than RBC aggregates from a control population, with no relation with either fibrinogen concentration or von-Willebrand factor antigen. In addition, in the same study, we found a lower nitric oxide production during the late recovery of a submaximal exercise in SCT carriers as compared to a control group. That suggests that impaired blood rheology in SCT carriers could be not very well compensated by vasoregulation. Further studies are clearly needed to know whether these blood rheological abnormalities really increase the risk of exercise-sudden death in SCT carriers. Nevretheless, a recent case study reporting central retinal vein occlusion induced by exercise and followed by a neovascular glaucoma in a SCT carriers with severe impairment in RBC deformability support that blood rheological abnormalities, in association with environmental strain (heat and warm exposure) could pay a role in microcirculatory disorders (Hedreville et al, 2009). In parallel, we are currently investigating the cardio-respiratory responses of SCT carriers which are known to sometimes differ with the responses oberved in non-SCT carriers (Connes et al, 2006). Scientific Collaborations: - Center of Sickle Cell Disease “Guy Mérault”, Academic Hospital of Pointe-a-Pitre, Guadeloupe - Department of Cardiology, Academic Hospital of Pointe-a-Pitre, Guadeloupe - Department of Hematology/Immunology, Academic Hospital of Pointe-a-Pitre, Guadeloupe - Dr John H. Boucher, Rheotech Labs, Inc. 2106 Salisbury Road, Silver Spring, MD 20910 Hemorheology and sickle cell disease Many works have been performed to describe blood rheology in sickle cell disease and all of them described alterations in RBC deformability. However, few works also suggested increased RBC aggregation. Therefore, RBC aggregation properties might play a role in the clinical manifestations and severity of the disease. We conducted a study in collaboration with Pr Herbert Meiselman and Dr Tamas Alexy (Los Angeles, Keck Medical School) focusing mainly on RBC aggregation in sickle cell disease. Main results demonstrated lower RBC aggregation index but higher disaggregation threshold shear rate in sickle cell patients as compared with healthy population (Tripette et al, in press). In addition, blood rheological profile and associations with different clinical manifestations of the disease are under investigations. We also started to assess the effects of different molecules on RBC rheology of sickle cell patients. At least, studies investigating the blood rheological responses during exercise in sickle cell patients are planned for the future. Scientific Collaborations: - Center of Sickle Cell Disease “Guy Mérault”, Academic Hospital of Pointe-a-Pitre, Guadeloupe - Department of Hematology/Immunology, Academic Hospital of Pointe-a-Pitre, Guadeloupe - Pr Herbert Meiselman and Dr Tamas Alexy, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA - Pr Cage Johnson, Comprehensive Sickle Cell Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA - Dr Max Hardeman, Department of Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands - Pr Harvey Reid, Department of Basic Sciences (Physiology Section), Faculty of Medical Sciences, University of the West Indies, Mona Kingston, Jamaica Hemodynamical parameters and hemorheology Although Poiseuille' equation predicts a great role of vascular hindrance on total vascular resistance (TVR), few works also demonstrated a role of blood rheology on TVR. For example, works from Shu Chien (in the 1970s) and works of Kalman Toth (1990s) provided evidences of involvement of blood rheology in hemodynamic responses. Based on integrative approach, we investigate the relationships between blood rheology (blood properties and red blood cell properties), hemodynamical parameters (cardiac output, total vascular resistance) and metabolism responses, such as VO2 responses. This approach will be used for different kind of populations, at rest and during exercise. - Department of Hematology/Immunology, Academic Hospital of Pointe-a-Pitre, Guadeloupe - Department of Cardiology, Academic Hospital of Pointe-a-Pitre, Guadeloupe - Pr Herbert Meiselman, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA Hemorheology and methodology
- Pr Daniel Le Gallais, Faculty of Medecine, Laboratory of Cardiovascular Physiology and Anesthesiology, 30907 Nîmes, France
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