Camille Faes

Ventilation, Oxidative Stress, and Nitric Oxide in Hypobaric versus Normobaric Hypoxia

PURPOSE Slight differences in physiological responses and nitric oxide (NO) have been reported at rest between hypobaric hypoxia (HH) and normobaric hypoxia (NH) during short exposure.Our study reports NO and oxidative stress at rest and physiological responses during moderate exercise in HH versus NH. METHODS Ten subjects were randomly exposed for 24 h to HH (3000 m; FIO2, 20.9%; BP, 530 ± 6 mm Hg) or to NH (FIO2, 14.7%; BP, 720 ± 1 mm Hg). Before and every 8 h during the hypoxic exposures, pulse oxygen saturation (SpO2), HR, and gas exchanges were measured during a 6-min submaximal cycling exercise. At rest, the partial pressure of exhaled NO, blood nitrate and nitrite (NOx), plasma levels of oxidative stress, and pH levels were additionally measured. RESULTS During exercise, minute ventilation was lower in HH compared with NH (-13% after 8 h, P < 0.05). End-tidal CO2 pressure was lower (P < 0.01) than PRE both in HH and NH but decreased less in HH than that in NH (-25% vs. -37%, P < 0.05).At rest, exhaled NO and NOx decreased in HH (-46% and -36% after 24 h, respectively, P < 0.05) whereas stable in NH. By contrast, oxidative stress was higher in HH than that in NH after 24 h (P < 0.05). The plasma pH level was stable in HH but increased in NH (P < 0.01). When compared with prenormoxic values, SpO2, HR, oxygen consumption, breathing frequency, and end-tidal O2 pressure showed similar changes in HH and NH. CONCLUSION Lower ventilatory responses to a similar hypoxic stimulus during rest and exercise in HH versus NH were sustained for 24 h and associated with lower plasma pH level, exaggerated oxidative stress, and impaired NO bioavailability.

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.

Moderate endurance exercise in patients with sickle cell anaemia: effects on oxidative stress and endothelial activation

Very few studies have investigated the effects of exercise on the biological parameters involved in vaso‐occlusive events in sickle cell anaemia (SCA). The aim of this study was to test how a mild‐moderate endurance exercise modulates oxidative stress, nitric oxide bioavailability and endothelial activation in SCA patients and healthy individuals. Eleven patients with SCA and 15 healthy subjects completed a 20‐min duration submaximal cycling exercise at ≈45 Watts. Plasma markers of oxidative stress, antioxidant activity, endothelial activation and nitric oxide bioavailability were investigated before and after the exercise. Nitric oxide levels, anti‐oxidant capacity, soluble (s)E‐selectin and sP‐selectin did not change in response to this exercise. Except for the malondialdehyde levels, which increased in the two groups, the other markers of oxidative stress remained unchanged in both groups in response to exercise. Soluble vascular cell adhesion molecule 1 levels were increased at the end of exercise in both groups. sL‐selectin decreased and soluble intercellular adhesion molecule 1 increased with exercise in SCA patients only. The present data suggest that patients with SCA may undertake mild‐moderate physical activities without any acute clinical complications, but care should be taken because oxidative stress and endothelial activation significantly increased in some patients.

Oxidative stress is decreased in physically active sickle cell SAD mice

Oxidative stress plays a crucial role in sickle cell disease (SCD) physiopathology. Given that chronic physical activity is known to decrease reactive oxygen species (ROS) and increase nitric oxide (NO) bioavailability in healthy subjects and in patients with cardiovascular or inflammatory pathologies, modulating these factors involved in the severity of the pathology could also be beneficial in SCD. This study aimed to determine if 8 weeks of increased physical activity (PA) by voluntary wheel running affects the hypoxia/reoxygenation (H/R) responses by reducing oxidative stress and increasing NO synthesis in sickle SAD mice. Nitrite/nitrate (NOx) concentrations, NOS3 mRNA expression and phosphorylated‐endothelial nitric oxide synthase immunostaining were increased in the lungs of the PA groups after H/R stress. Moreover, lipid peroxidation in the heart was decreased in PA SAD mice. The improvement of antioxidant activity at rest and the decrease in haemolysis may explain this reduced oxidative stress. These results suggest that physical activity probably diminishes some deleterious effects of H/R stress in SAD mice and could be protective against vascular occlusions.

Effect of Age on Blood Rheology in Sickle Cell Anaemia and Sickle Cell Haemoglobin C Disease: A Cross-Sectional Study

Objectives Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown. Materials and Methods Blood viscosity, red blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients. Results Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age. Conclusion The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.

Importance of methodological standardization for the ektacytometric measures of red blood cell deformability in sickle cell anemia.

Red blood cell (RBC) deformability is severely decreased in patients with sickle cell anemia (SCA), which plays a role in the pathophysiology of the disease. However, investigation of RBC deformability from SCA patients demands careful methodological considerations. We assessed RBC deformability by ektacytometry (LORRCA MaxSis, Mechatronics, The Netherlands) in 6 healthy individuals and 49 SCA patients and tested the effects of different heights of the RBC diffraction patterns, obtained by altering the camera gain of the LORRCA, on the result of RBC deformability measurements, expressed as Elongation Index (EI). Results indicate that the pattern of RBCs from control subjects adopts an elliptical shape under shear stress, whereas the pattern of RBCs from individuals with SCA adopts a diamond shape arising from the superposition of elliptical and circular patterns. The latter represent rigid RBCs. While the EI measures did not change with the variations of the RBC diffraction pattern heights in the control subjects, we observed a decrease of EI when the RBC diffraction pattern height is increased in the SCA group. The differences in SCA EI values measured at 5 Pa between the different diffraction pattern heights correlated with the percent of hemoglobin S and the percent of sickled RBC observed by microscopy. Our study confirms that the camera gain or aperture of the ektacytometer should be used to standardize the size of the RBC diffraction pattern height when measuring RBC deformability in sickle cell patients and underscores the potential clinical utility of this technique.

Physical activity limits pulmonary endothelial activation in sickle cell SAD mice

To the editor: Vaso-occlusion (VOC) in sickle cell disease (SCD) results from many pathophysiological mechanisms including sickling of red blood cells, hemolysis, inflammation, vascular adhesion, and reduced nitric oxide (NO) bioavailability.[1][1] All these mechanisms interact together to trap

Alpha‐thalassaemia promotes frequent vaso‐occlusive crises in children with sickle cell anaemia through haemorheological changes

Sickle cell anaemia (SCA) is a severe hereditary haemoglobinopathy characterised by haemorheological abnormalities, which play a role in the occurrence of several acute and chronic clinical complications. While βS‐haplotypes and alpha‐thalassaemia modulate SCA clinical severity, their effects on blood rheology have been incompletely described. The aim of this study was to test the effects of these genetic modifiers on the haemorheological properties and clinical complication of children with SCA.

Chronic physical activity limits blood rheology alterations in transgenic SAD mice

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Does physical activity increase or decrease the risk of sickle cell disease complications

Sickle cell disease (SCD) is the most common inherited disease in the world. Red blood cell sickling, blood cell-endothelium adhesion, blood rheology abnormalities, intravascular haemolysis, and increased oxidative stress and inflammation contribute to the pathophysiology of SCD. Because acute intense exercise may alter these pathophysiological mechanisms, physical activity is usually contra-indicated in patients with SCD. However, recent studies in sickle-cell trait carriers and in a SCD mice model show that regular physical activity could decrease oxidative stress and inflammation, limit blood rheology alterations and increase nitric oxide metabolism. Therefore, supervised habitual physical activity may benefit patients with SCD. This article reviews the literature on the effects of acute and chronic exercise on the biological responses and clinical outcomes of patients with SCD.