Lower Muscle and Blood Lactate Accumulation in Sickle Cell Trait Carriers in Response to Short High-Intensity Exercise.

It remains unclear whether sickle cell trait (SCT) should be considered a risk factor during intense physical activity. By triggering the polymerization-sickling-vaso-occlusion cascade, lactate accumulation-associated acidosis in response to high-intensity exercise is believed to be one of the causes of complications. However, our understanding of lactate metabolism in response to high-intensity exercise in SCT carriers is incomplete. Thirty male SCT carriers (n = 15) and healthy subjects (n = 15) with and without α-thalassemia performed a 2-min high-intensity exercise. Blood and muscle lactate concentrations were measured at exercise completion. Time courses of blood lactate and glucose concentrations were followed during the subsequent recovery. Additional biochemical analyses were performed on biopsies of the vastus lateralis muscle. SCT was associated with lower blood and muscle lactate concentrations in response to the short high-intensity exercise. Compared to controls, the muscle content among SCT carriers of lactate transporter MCT4 and ß2-adrenergic receptor were higher and lower, respectively. During recovery, the lactate removal ability was higher in SCT carriers. In the present study, no effect of α-thalassemia was observed. The lower blood and muscle lactate accumulations in SCT carriers may, to some extent, act as protective mechanisms: (i) against exercise-related acidosis and subsequent sickling, that may explain the relatively rare complications observed in exercising SCT carriers; and (ii) against the deleterious effects of intracellular lactate and associated acidosis on muscle function, that might explain the elevated presence of SCT carriers among the best sprinters.

Effects of regular physical activity on skeletal muscle structural, energetic, and microvascular properties in carriers of sickle cell trait.

To assess the effects of regular physical activity on muscle functional characteristics of carriers of sickle cell trait (SCT), 39 untrained (U) and trained (T) hemoglobin (Hb)AA (CON) and SCT subjects (U-CON, n = 12; U-SCT, n = 8; T-CON, n = 10; and T-SCT, n = 9) performed a graded exercise and a time to exhaustion (T(ex)) test, and were subjected to a muscle biopsy. Maximal power, total work performed during T(ex), citrate synthase and cytochrome c oxidase (COX) activities, respiratory chain complexes I and IV content, and capillary density (CD), diameter (COD), and surface area (CSA) were upregulated by the same proportion in T-CON and T-SCT compared with their untrained counterparts. These proportionally similar differences imply that the observed discrepancies between U-SCT and U-CON remained in the trained subjects. Specifically, both CD and COX remained and tended to remain lower, and both COD and CSA remained and tended to remain higher in T-SCT than in T-CON. Besides, carriers of SCT displayed specific adaptations with regular physical activity: creatine kinase activity; complexes II, III, and V content; and type I fiber surface area and capillary tortuosity were lower or unchanged in T-SCT than in U-SCT. In summary, our results show that 1) carriers of SCT adapted almost similarly to CON to regular physical activity for most of the studied muscle characteristics, 2) oxidative potential remains altered in physically active carriers of SCT compared with HbAA counterparts, and 3) the specific remodeling of muscle microvascular network persists in the trained state.

Exercise training blunts oxidative stress in sickle cell trait carriers.

The aim of this study was to analyze the effects of exercise training on oxidative stress in sickle cell trait carriers. Plasma levels of oxidative stress [advanced oxidation protein products (AOPP), protein carbonyl, malondialdehyde (MDA), and nitrotyrosine], antioxidant markers [catalase, glutathione peroxidase (GPX), and superoxide dismutase (SOD)], and nitrite and nitrate (NOx) were assessed at baseline, immediately following a maximal exercise test (T(ex)), and during recovery (T(1h), T(2h), T(24h)) in trained (T: 8 h/wk minimum) and untrained (U: no regular physical activity) sickle cell trait (SCT) carriers or control (CON) subjects (T-SCT, n = 10; U-SCT, n = 8; T-CON, n = 11; and U-CON, n = 11; age: 23.5 ± 2.2 yr). The trained subjects had higher SOD activities (7.6 ± 5.4 vs. 5.2 ± 2.1 U/ml, P = 0.016) and lower levels of AOPP (142 ± 102 vs. 177 ± 102 µM, P = 0.028) and protein carbonyl (82.1 ± 26.0 vs. 107.3 ± 30.6 nm/ml, P = 0.010) than the untrained subjects in response to exercise. In response to exercise, U-SCT had a higher level of AOPP (224 ± 130 vs. 174 ± 121 µM, P = 0.012), nitrotyrosine (127 ± 29.1 vs.70.6 ± 46.6 nM, P = 0.003), and protein carbonyl (114 ± 34.0 vs. 86.9 ± 26.8 nm/ml, P = 0.006) compared with T-SCT. T-SCT had a higher SOD activity (8.50 ± 7.2 vs. 4.30 ± 2.5 U/ml, P = 0.002) and NOx (28.8 ± 11.4 vs. 14.6 ± 7.0 µmol·l(-1)·min(-1), P = 0.003) in response to exercise than U-SCT. Our data indicate that the overall oxidative stress and nitric oxide response is improved in exercise-trained SCT carriers compared with their untrained counterparts. These results suggest that physical activity could be a viable method of controlling the oxidative stress. This could have a beneficial impact because of its involvement in endothelial dysfunction and subsequent vascular impairment in hemoglobin S carriers.

Skeletal muscle structural and energetic characteristics in subjects with sickle cell trait, alpha-thalassemia, or dual hemoglobinopathy.

Previous studies have shown that subjects with sickle cell trait (SCT), alpha-thalassemia (alpha-t), and the dual hemoglobinopathy (SCT/alpha-t) manifest subtle, albeit significant, differences during exercise. To better understand such differences, we assessed skeletal muscle histomorphological and energetic characteristics in 10 control HbAA subjects (C), 5 subjects with alpha-t (alpha-t), 6 SCT carriers (SCT) and 9 SCT carriers with alpha-t (SCT/alpha-t). Subjects underwent a muscle biopsy and also performed an incremental maximal exercise and a time to exhaustion test. There were no observable differences in daily energy expenditure, maximal power output (Pmax), or time to exhaustion at 110% Pmax (Tex) among the groups. Blood lactate concentrations measured at the end of the Tex, muscle fiber type distribution, and mean phosphofructokinase (PFK), lactate dehydrogenase (LDH), beta-hydroxyacyl-CoA-dehydrogenase (HAD), and citrate synthase (CS) activities were all similar among the four groups. However, SCT was associated with a lower cytochrome-c oxidase (COx) activity in type IIa fibers (P<0.05), and similar trends were observed in fiber types I and IIx. Trends toward lower creatine kinase (CK) activity (P=0.0702) and higher surface area of type IIx fibers were observed in SCT (P=0.0925). In summary, these findings support most of the previous observations in SCT, such as 1) similar maximal power output and associated maximal oxygen consumption (VO2max) values and 2) lower exercise performances during prolonged submaximal exercise. Furthermore, performances during short supramaximal exercise were not different in SCT. Finally, the dual hemoglobinopathy condition does not seem to affect muscle characteristics.

Habitual physical activity and endothelial activation in sickle cell trait carriers.

PURPOSE: It remains unclear whether habitual physical activity in sickle cell trait (SCT) carriers modulates the levels of resting and postexercise vascular adhesion and inflammatory molecules. METHODS: Plasma levels of pro-inflammatory (interleukin (IL)-4, IL-5, IL-8, sCD40L, and tumor necrosis factor α) and anti-inflammatory (IL-10) cytokines and adhesion molecules (soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), sP-selectin, or sE-selectin) were assessed at rest and in response to an incremental exercise to exhaustion in untrained (UT: no regular physical activity) and trained (T: soccer players, 8 h·wk minimum) SCT and control (CON) subjects (n = 8 per group; age = 23.5 ± 0.35 yr). RESULTS: sVCAM-1 levels were significantly higher in the UT-SCT group than that in T-SCT group (+43.5%) at rest, at the end, and at 1, 2, and 24 h after the end of the exercise. For the other molecules, no differences emerged among the groups at rest, but in response to exercise plasma, sICAM-1, sVCAM-1, sE-selectin, and sCD40L increased in all groups, and sP-selectin only increased in the UT group. All values that increased with the acute exercise returned to their respective baseline levels 1 h after the end of the exercise. CONCLUSIONS: A physically active lifestyle in SCT carriers may decrease endothelial activation and may limit the risk for vascular adhesion events in the microcirculation of SCT subjects.

Remodeling of skeletal muscle microvasculature in sickle cell trait and alpha-thalassemia.

The influence of sickle cell trait and/or alpha-thalassemia on skeletal muscle microvascular network characteristics was assessed and compared with control subjects [hemoglobin (Hb) AA] in 30 Cameroonian residents [10 HbAA, 5 HbAA alpha-thalassemia (alpha-t), 6 HbAS, and 9 HbASalpha-t] matched for maximal work capacity and daily energy expenditure. Subjects performed an incremental exercise to exhaustion and underwent a muscle biopsy. Muscle fiber type and surface area were not different among groups. However, sickle cell trait (SCT) was associated with lower capillary density (P < 0.05), lower capillary tortuosity (P < 0.001), and enlarged microvessels (P < 0.01). SCT carriers had reduced counts of microvessels <5-microm diameter, but a higher percentage of broader microvessels, i.e., diameter >10 microm (P < 0.05). alpha-Thalassemia seemed to be characterized by a higher capillary tortuosity and unchanged capillary density and diameter. Thus, while SCT is a priori clinically benign, we demonstrate for the first time that significant remodeling of the microvasculature occurs in SCT carriers. These modifications may possibly reflect protective adaptations against hemorheological and microcirculatory dysfunction induced by the presence of HbS. The remodeling of the microvascular network occurs to a lesser extent in alpha-thalassemia. In alpha-thalassemic subjects, increased capillary tortuosity would promote oxygen supply to muscle tissues and might compensate for the lower Hb content often reported in those subjects.

Enhancement of mental rotation abilities and its effect on anatomy learning.

BACKGROUND: Mental rotation (MR) is improved through practice and high MR ability is correlated to success in anatomy learning. PURPOSES: We investigated the effects of improving the MR ability on the Vandenberg and Kuse MR test performance and the consequences on learning functional human anatomy. METHODS: Forty-eight students were assigned into three groups: MR group (16 students attending functional anatomy course and MR training), anatomy group (16 students attending the same functional anatomy course), and the control group (n = 16). Instead of MR training, the latter 2 groups were engaged in physical activities for an equivalent time, and the control group did not attend anatomy course. RESULTS: MR group performed better than the two others in the MR test and better than the anatomy group in the anatomy test. CONCLUSIONS: The MR training sessions were found to improve MR test performance and were further transferred to anatomy learning.

Plasma levels of adhesion molecules ICAM-1 and VCAM-1 in athletes with sickle cell trait with or without alpha-thalassemia during endurance exercise and recovery.

The aim of the study was to examine the effects of endurance exercise on circulating vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in sickle cell trait (SCT) athletes with or without alpha-thalassemia. Five athletes with SCT, 7 athletes with both SCT and alpha-thalassemia (SCTAT) and 8 control athletes (CONT) performed an incremental test on cycloergometer followed 72 hours later by a 60-min endurance exercise with a workload set at 70% P(peak) (peak power). We assessed levels of sICAM-1, sVCAM-1 and TNF-alpha at rest, immediately after endurance exercise and 1, 2, and 24 hours of recovery. Although, CONT and SCTAT groups exhibited similar basal plasma levels of adhesion molecules and TNF-alpha, SCT group had higher sVCAM-1 basal concentrations. No significant variation in sVCAM-1, sICAM-1 and TNF-alpha was measured following endurance exercise. Consequently, sVCAM-1 remained elevated in the SCT group after exercise and during the recovery period. In conclusion, our findings support the concept that SCT athletes might be at risk for microcirculatory disturbances, but these adhesive processes were not further impaired in response to endurance exercise. In addition, alpha-thalassemia co existing trait may be protective both at rest and after endurance exercise in SCT subjects.

Relationship between spatial abilities, mental rotation and functional anatomy learning.

This study investigated the relationship between visuo-spatial representation, mental rotation (MR) and functional anatomy examination results. A total of 184 students completed the Group Embedded Figures Test (GEFT), Mental Rotation Test (MRT) and Gordon Test of Visual Imagery Control. The time spent on personal assignment was also considered. Men were found to score better than women on both GEFT and MRT, but the gender effect was limited to the interaction with MRT ability in the anatomy learning process. Significant correlations were found between visuo-spatial, MR abilities, and anatomy examination results. Data resulting from the best students' analyzes underscore the effect of high MR ability which may be considered reliable predictor of success in learning anatomy. The use of specific tests during learning sessions may facilitate the acquisition of anatomical knowledge.

Effects of progressive and maximal exercise on plasma levels of adhesion molecules in athletes with sickle cell trait with or without alpha-thalassemia.

The aim of the study was to examine the effects of exercise on soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in sickle cell trait (SCT) athletes with or without alpha-thalassemia. Six athletes with SCT, seven athletes with both SCT and alpha-thalassemia (SCTAT), and seven control athletes (Cont) performed an incremental and maximal test on cycloergometer. Levels of sICAM-1 and sVCAM-1 were assessed at rest, immediately after the end of exercise, and 1, 2, and 24 h after exercise. Although Cont and SCTAT groups exhibited similar basal plasma levels of inflammatory and adhesion molecules, the SCT group had higher sVCAM-1 basal concentrations. Incremental exercise resulted in a significant increase of sVCAM-1 in all subjects, which remained elevated only in the SCT group during the recovery period. In conclusion, as sVCAM-1 increased with exercise and during the recovery period, our findings support the concept that SCT athletes might be at risk for microcirculatory disturbances and adhesive phenomena developing at rest and several hours after exercise. alpha-Thalassemia might be considered protective among exercising SCT subjects.

Nocturnal autonomic nervous system activity impairment in sickle cell trait carriers.

Sickle cell trait (SCT) is a genetic disease affecting the synthesis of normal haemoglobin (Hb) and marked by the heterozygous presence of HbA and HbS. Some studies have suggested that SCT carriers might be prone to vascular alterations, cardiac ischaemia and arrhythmias leading, in some subjects, to sudden death. It is well known that a loss or a disequilibrium of autonomic activity are powerful predictors of sudden cardiac death. We hypothesized that SCT subjects might exhibit alterations in the activity of the autonomic nervous system that could constitute further risk factors for cardiac complications. Resting haemorheological parameters (eta(b), blood viscosity; eta(p), plasma viscosity; Hct, haematocrit; Tk, red blood cell rigidity), and sympathetic and parasympathetic indices of nocturnal autonomic activity (temporal and frequency analysis of heart rate variability) were thus compared between a group of nine SCT subjects and a group of nine control subjects. eta(b) was higher in the SCT group than in the control group while Hct, eta(p) and Tk were not different. Global variability (SDNN, SDNNIDX) and parasympathetic (PNN50, RMSSD, HF) indices were significantly lower in the SCT group compared with the control group, while the LF/HF ratio was highly increased, underlining a major sympathetic shift. The autonomic imbalance in SCT subjects was mainly related to lowered parasympathetic activity. Thus, our study suggests an additional global decrease and imbalance of autonomic nervous system activity to biological disorders of SCT carriers, that may constitute further risk factors for cardiac complications in this population.

Hemorheology, sickle cell trait, and alpha-thalassemia in athletes: effects of exercise.

PURPOSE: This study investigated hemorheological parameters in response to exercise in sickle cell trait (SCT) athletes with or without alpha-thalassemia METHODS: Six athletes with SCT (HbAS), 7 athletes with SCT and alpha-thalassemia (HbASAT), and 10 control athletes (HbAA) performed a progressive and maximal exercise test on cycloergometer. Blood viscosity (etab), plasma viscosity (etap), etab at corrected hematocrit (etab45), hematocrit (Hct), and red blood cell (RBC) rigidity were assessed at rest, at maximal exercise and 24 h after exercise RESULTS: etab and etap were not different between the three groups at any time. Exercise induced changes in etab in HbAA and HbASAT groups but not in HbAS group. etab45 was higher in HbAS group compared with the other groups (P < 0.05), at rest and 24 h after exercise and increased only in HbAA group in response to exercise. HbAS group had lower Hct than HbAA group at any time. Hct and etap increased after exercise and declined under baseline values 24 h after exercise in all groups. RBC rigidity was higher in HbAS group compared with HbAA and HbASAT groups at any time, and was lower and higher at maximal exercise and 24 h after exercise, respectively, in all groups compared with resting values CONCLUSIONS: These results demonstrate that HbAS group is prone to higher RBC rigidity, which might lead to hemorheological alterations that are thought to participate to microcirculation disorders. However, these alterations are limited by the coexistence of alpha-thalassemia. Moreover, hemorheological parameters were not further impaired in SCT athletes with or without alpha-thalassemia in response to exercise. Training status might be protective from physiological stresses usually leading to sickling process in SCT carriers.

Kinetics of anaerobic metabolism in human skeletal muscle: influence of repetitive high-intensity exercise on sedentary dominant and non-dominant forearm. A 31P NMR study.

Potential differences were assessed between the dominant (D) and non-dominant (ND) forearms of sedentary subjects during anaerobic exercise. Subjects performed voluntary concentric contractions of D and ND forearm muscle during a series of three high-intensity (60% of the maximal voluntary contraction force (MVC)) exercise bouts. The time-dependent changes in intracellular pH (pH(i)), Pi, and PCr concentrations, and their relation to muscular work were examined using 31P magnetic resonance spectroscopy (MRS) techniques, and revealed that D forearm metabolic kinetics in sedentary individuals are improved during repetitive high-intensity exercise compared to their respective ND forearm muscle. We postulate that the more regular and preferential utilization of the D limb leads to a "trained-like" condition.