Patterns of exercise-related inflammatory response in sickle cell trait carriers.

OBJECTIVE: To clarify whether sickle cell trait (SCT) carriers (SCT group) present a specific postexercise inflammatory response to repeated and strenuous exercise. DESIGN: The patterns of inflammatory markers in response to repeated heavy exercise were investigated in SCT carriers (SCT group: eight men, 20.0+/-0.7 years) and subjects with normal haemoglobin (CONT group: seven men, 20.6+/-0.7 years). The exercise consisted of three successive maximal ramp exercise tests, interspaced with 10 min of recovery, and accomplished at room temperature. Blood was sampled at rest (T(R)), at the end of each of the three tests (T(1), T(2), T(3)) and during the immediate (T(1 h), T(2 h)) and late (T(24 h), T(48 h)) recovery periods. Standard haematological parameters and plasma levels of cytokines (TNFalpha, IL-6) and adhesion molecules: soluble L- and P-selectins (sL-selectin, sP-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1) were measured. RESULTS: In both groups, the three successive maximal exercise bouts prompted an inflammatory response (ie, white blood cells and IL-6 levels increased in response to exercise). sICAM-1 and sVCAM-1 levels did not change during or after exercise and presented no difference between groups. However, during exercise, sL-selectin and sP-selectin kinetics differed between groups: sL-selectin increased earlier in the SCT group than in the CONT group, and sP-selectin statistically increased only in the SCT group. CONCLUSION: Although the data do not indicate an extended exercise inflammatory response in SCT carriers, a specific activation of the L- and P-selectins was observed. Further studies are needed to determine whether the selectins' changes are evidence of greater risk for SCT carriers during physical exercise in specific conditions or an indication of a protective mechanism mediated by the shedding process of adhesion molecules.

Cardiorespiratory responses during three repeated incremental exercise tests in sickle cell trait carriers.

This study investigated the cardioventilatory responses during heavy exercise in sickle cell trait carriers (SCTc) and subjects with normal hemoglobin (control group). Eight SCTc and six control subjects repeated three incremental exercise tests (Iet) separated by 10-min recoveries. Cardioventilatory parameters were analyzed at rest and during the first and third Iet. No significant difference in the ventilatory parameters [notably, maximal oxygen uptake (VO2max) and the ventilatory thresholds] was observed between the two groups. The time course of power output showed a significant difference between the first and third Iet from 80% of VO2max to VO2max (P < 0.05) in both groups. In conclusion, SCTc exhibited normal ventilatory responses during three successive Iet, which strongly suggests that this population, despite the presence of HbS in their red blood cells, is not limited during this type of aerobic exercise.

Faster lactate transport across red blood cell membrane in sickle cell trait carriers.

The physical and physiological behavior of sickle cell trait carriers (AS) is somewhat equivocal under strenuous conditions, although this genetic abnormality is generally considered to be a benign disorder. The occurrence of incidents and severe injuries in AS during exercise might be explained, in part, by the lactic acidosis due to a greater lactate influx into AS red blood cells (RBCs). In the present study, the RBC lactate transport activity via the different pathways was compared between AS and individuals with normal hemoglobin (AA). Sixteen Caribbean students, nine AS and seven AA, performed a progressive and maximal exercise test to determine maximal oxygen consumption. Blood samples were obtained at rest to assess haematological parameters and RBC lactate transport activity. Lactate influxes [total lactate influx and monocarboxylate transporter (MCT-1)-mediated lactate influx] into erythrocytes were measured at four external [14C]-labeled lactate concentrations (1.6, 8.1, 41, and 81.1 mM). The two groups had similar maximal oxygen consumption. Total lactate influx and lactate influx via the MCT-1 pathway were significantly higher in AS compared with AA at 1.6, 41, and 81.1 mM. The maximal lactate transport capacity for MCT-1 was higher in AS than in AA. Although AS and AA had the same maximal aerobic physical fitness, the RBCs from the sickle cell trait carriers took up more lactate at low and high concentrations than the RBCs from AA individuals. The higher MCT-1 maximal lactate transport capacity found in AS suggests greater content or greater activity of MCT-1 in AS RBC membranes.

Impaired oxygen uptake efficiency slope and off-transient kinetics of pulmonary oxygen uptake in sickle cell anemia are associated with hemorheological abnormalities.

Oxygen uptake efficiency slope (OUES) and excess post-exercise oxygen consumption (EPOC) are markers of physical fitness in the general population but have never been characterized in sickle cell anemia (SCA) where hematological and hemorheological properties are severely altered. Eight SCA patients and eleven healthy subjects (CONT) performed a submaximal incremental exercise conducted until the first ventilatory threshold (VT1). OUES was calculated from the data collected during the incremental period and EPOC parameters (amplitude [A] and time constant [τ]) were calculated from the data measured during exercise recovery. We found that OUES (p = 0.007) and A (p = 0.010) were lower, and τ (p = 0.035) was higher, in SCA patients compared to CONT subjects. OUES and τ were significantly correlated with hematocrit, red blood cell (RBC) deformability and RBC aggregates strength. Our findings suggest that both the abilities to use oxygen during exercise and to recover after a physical activity are impaired in SCA patients. This poor physical fitness seems to depend on the degree of anemia and RBC rheological alterations.

Acute moderate exercise does not further alter the autonomic nervous system activity in patients with sickle cell anemia.

A decreased global autonomic nervous system (ANS) activity and increased sympathetic activation in patients with sickle cell anemia (SCA) seem to worsen the clinical severity and could play a role in the pathophysiology of the disease, notably by triggering vaso-occlusive crises. Because exercise challenges the ANS activity in the general population, we sought to determine whether a short (<15 min) and progressive moderate exercise session conducted until the first ventilatory threshold had an effect on the ANS activity of a group of SCA patients and a group of healthy individuals (CONT group). Temporal and spectral analyses of the nocturnal heart rate variability were performed before and on the 3 nights following the exercise session. Standard deviation of all normal RR intervals (SDNN), total power, low frequencies (LF) and high frequencies powers (HF) were lower but LF/HF was higher in SCA patients than in the CONT group. Moderate exercise did not modify ANS activity in both groups. In addition, no adverse clinical events occurred during the entire protocol. These results imply that this kind of short and moderate exercise is not detrimental for SCA patients.

Delayed beneficial effect of acute exercise on red blood cell aggregate strength in patients with sickle cell anemia.

Because of the metabolic changes induced by a physical activity, the hemorheological properties of patients with sickle cell anemia could be further impaired and increase the risks for vaso-occlusive complications. However, few studies suggest that moderate physical activity could be beneficial rather than harmful in patients with sickle cell anemia (SCA). However, the definition of what can be considered as a moderate physical activity in SCA patients is imprecise. The present study tested the effects of a short incremental cycling exercise test conducted until the first ventilatory threshold on different biomarkers. Hematological and hemorheological parameters were compared between 8 patients with SCA and 13 healthy subjects (CONT) before, immediately after the end of the exercise and at 12, 36 and 60 hours after the exercise. We observed no significant hematological or hemorheological alteration induced by the exercise in the two groups. However, the exercise resulted in a delayed improvement of the red blood cell disaggregation threshold at 36 and 60 hrs after exercise in the SCA group which was paralleled to the decrease in the platelet count in this group. The present study suggests that such an exercise might be beneficial for microcirculatory blood flow.

Endurance running trial in tropical environment: a blood rheological study.

PURPOSE: The aim of this study was to clarify whether exercising in a tropical climate induces blood rheology alterations despite ad libitum hydration. METHODS: Hematological, biochemical and hemorheological changes were investigated in young healthy adults (N = 9 men, 20.7 ± 0.8 yrs) after a 10-km race in hot and humid conditions. Subjects' maximal aerobic abilities were tested using a maximal ramp exercise. Blood was sampled at rest (TR), at the end of the race (TEx), and after 24 hours of recovery (T24). Ad libitum hydration was allowed during the race. Blood viscosity (ηb), red blood cell deformability (EI), aggregation (AI) and disaggregation shear rate (γ) were measured. RESULTS: Hematocrit, hemoglobin and plasma concentration of chlorine, sodium and potassium did not change in response to exercise. No functional consequence was observed on RBC deformability since EI remained unchanged. Percentages of echinocytes, schizocytes and stomatocytes remained in the subclinical range at all times. AI, γ and ηb did not present change. CONCLUSION: Running exercise in tropical climate with ad libitum hydration does not alter the main rheological properties of blood.

Central retinal vein occlusion in a sickle cell trait carrier after a cycling race.

A 26-yr-old man with sickle cell trait (SCT) suddenly lost visual acuity in the left eye after a cycling race in hot tropical environment. The cause was massive central retinal vein occlusion (CRVO) with hemorrhaging that rapidly worsened to neovascular glaucoma. Although medically treated, the eye is now marked by total retinal detachment. Cardiovascular function assessment shows no electrocardiographic abnormalities, no anomaly in the supra-aortic tree, and no evidence of structural heart disease. Although normal coagulation markers values (i.e., activated partial thromboplastin time, prothrombin time, fibrinogen concentration, antithrombin III, factor V, proteins C and S) were observed 2.5 months after the clinical event, a transesophageal echocardiogram performed few hours after the incident revealed the presence of four thrombi in the left atrium suggesting a postexercise hypercoagulable state at that time. Hemorheological measurements at distance of the events demonstrated high red blood cell rigidity at baseline. Therefore, marked blood rheological impairment and activation of the coagulation pathway in response to the heavy and prolonged cycling race could have promoted CRVO in this cyclist carrying SCT. These data suggest that SCT could be considered as a risk factor for significant ocular complications when severe exercise is performed and support the idea that SCT is a contributing factor in blood rheology and vascular dysfunctions.

Effects of strenuous exercise on autonomic nervous system activity in sickle cell trait carriers.

This study compared the nocturnal autonomic nervous system (ANS) activity in seven sickle cell trait (SCT) carriers and six subjects with normal hemoglobin in response to exercise Sympathetic and parasympathetic indices of nocturnal ANS were measured in the two groups before and 24 and 48 h after a strenuous exercise consisting of the repetition of three maximal exercise bouts. Global ANS activity decreased 24 h after exercise in both groups and was lower before as well as after exercise in SCT carriers. Indices of parasympathetic activity were lower in SCT carriers at all times, indicating a persistent sympatho-vagal imbalance. Exercise did not cause a rebound in parasympathetic activity in either group, but a rebound was noted for sympathetic index values two days after exercise in SCT group only. The ANS activity was generally lower, and the sympatho-vagal imbalance greater, in SCT carriers compared with control subjects irrespective of exercise and could increase the risk for medical complications in this population.

Does repeated and heavy exercise impair blood rheology in carriers of sickle cell trait?

OBJECTIVE: To determine if the time courses of hemorheologic parameters are different between carriers of sickle cell trait (SCT) and subjects with normal hemoglobin in response to exercise. DESIGN: Observational and comparative study. SETTING: Testing was conducted in a laboratory of exercise physiology. PARTICIPANTS: Nine carriers of sickle cell trait (SCT group) and 7 subjects with normal hemoglobin (CONT group) performed an exercise protocol of the repetition of 3 successive maximal ramp exercise tests. INTERVENTIONS: Blood was sampled at rest (TR), at the end of each of the 3 tests (T1, T2, T3), and during the immediate (T2h) and late (T24h, T48h) recovery periods. MAIN OUTCOME MEASUREMENTS: Blood and plasma viscosity (etab and etap, respectively), hematocrit (Hct), and red blood cell (RBC) rigidity (Tk and k indexes) were determined. RESULTS: In both groups, etab significantly increased in response to exercise but the SCT group had significantly higher etab at T3 and T2h. etab then returned to baseline value at T2h in the CONT group and at T24h in the SCT group. Tk and k were not changed by exercise but significantly increased above baseline value in both groups at T24h and T48h. The increase in Tk and k during late recovery was higher in the SCT group than in the CONT group, indicating that SCT carriers had significantly higher RBC rigidity than the CONT group at that time. CONCLUSIONS: The hemorheologic changes induced by exercise in the SCT carriers could trigger microcirculatory disorders during the recovery.