Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease?

Chatel, Benjamin; Messonnier, Laurent; Bendahan, David

doi:10.1113/ep087169

Cited by 14 publications

(21 citation statements)

References 76 publications

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“…However, lactate accumulation may be detrimental for patients. Indeed, increased blood lactate is accompanied by systemic acidosis 10 which in turn favors Hb polymerization, sickling and potentially VOC 13 . Skeletal muscle of SCD patients is also hypotrophic 6 and that is detrimental for force production 14 .…”

Section: Introductionmentioning

confidence: 99%

Muscle structural, energetic and functional benefits of endurance exercise training in sickle cell disease

et al. 2020

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Sickle cell disease (SCD) patients display skeletal muscle hypotrophy, altered oxidative capacity, exercise intolerance and poor quality of life. We previously demonstrated that moderate-intensity endurance training is beneficial for improving muscle function and quality of life of patients. The present study evaluated the effects of this moderate-intensity endurance training program on skeletal muscle structural and metabolic properties. Of the 40 randomized SCD patients, complete data sets were obtained from 33. The training group (n = 15) followed a personalized moderateintensity endurance training program, while the non-training (n = 18) group maintained a normal lifestyle. Biopsies of the vastus lateralis muscle and submaximal incremental cycling tests were performed before and after the training program. Endurance training increased type I muscle fiber surface area (P = .038), oxidative enzyme activity [citrate synthase, P < .001; β-hydroxyacyl-CoA dehydrogenase, P = .009; type-I fiber cytochrome c oxidase, P = .042; respiratory chain complex IV, P = .017] and contents of respiratory chain complexes I (P = .049), III (P = .005), IV (P = .003) and V (P = .002). Respiratory frequency, respiratory exchange ratio, blood lactate concentration and rating of perceived exertion were all lower at a given submaximal power output after training vs non-training group (all P < .05). The muscle content of proteins involved in glucose transport and pH regulation were unchanged in the training group relative to the non-training group. The moderate-intensity endurance exercise program improved exercise capacity and muscle structural and oxidative properties. This trial was registered at www.clinicaltrials.gov as #NCT02571088. 1 | INTRODUCTION Sickle cell disease (SCD) is the most frequent worldwide genetic disease. 1 This hemoglobinopathy results in synthesis of abnormal S hemoglobin (HbS) which may polymerize once deoxygenated, potentially resulting in the sickling of red blood cells (RBC). Sickle-shaped RBC are less deformable and adhere better to endothelium, 1 the combination of which may cause sickle RBC entrapment in the microcirculation. Entrapment of RBC may progress to painful vaso-occlusive crises (VOC), one of the main complications of the disease, 1 and may lead to failure of vital organs. 2 Sickle RBC are also fragile, causing hemolysis, release of free hemoglobin into circulation and severe chronic anemia. 1 SCD patients are often subjected to arterial †EXDRE collaborative study group

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Section: Introductionmentioning

confidence: 99%

Muscle structural, energetic and functional benefits of endurance exercise training in sickle cell disease

et al. 2020

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“…Many years ago, it was shown that adding hydrogen ions to blood reduces the oxygen-binding affinity of hemoglobin [78]. This means that pH can modulate the oxyhemoglobin dissociation profile, and, for a given oxygen pressure, acidosis results in a reduction in oxygen saturation [79]. These factors may explain the reason why the increase in VO 2max after the consumption of beetroot juice was not of a similar level in all of the studied fencers.…”

Section: Discussionmentioning

confidence: 90%

Changes in Oxidative Stress, Inflammation, and Muscle Damage Markers Following Diet and Beetroot Juice Supplementation in Elite Fencers

et al. 2020

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The aim of this study was to assess the impact of diet and active substances in beetroot juice on the parameters of oxidative stress, inflammation, and muscle damage as well as on the maximum rate of oxygen uptake (VO2max) in elite fencers (10 women, 10 men). Athletes during four weeks realized dietary recommendations (ID) and, after that, diet with freeze-dried beetroot juice supplementation (ID&BEET). At baseline and after each stage, fasting antioxidants, biomarkers of oxidative stress, inflammation, and skeletal muscle damage were measured, and a VO2max test was performed. Only after ID&BEET was a significant increase of VO2max observed, and changes of this parameter were negatively related with changes of serum lactate dehydrogenase (∆LDH) activity, as well as with serum ∆β-carotene and malondialdehyde concentration (∆MDA). Additionally, positive relationships were observed between ∆β-carotene versus changes of the serum concentration of advanced oxidation protein products (∆AOPP), changes of serum glutathione peroxidase activity (∆GPx3) versus both changes of physical activity level and ∆LDH, as well as erythrocyte glutathione peroxidase activity (∆GPx1) versus ∆LDH. To summarize, we showed that long-term beetroot juice supplementation increases lipid peroxidation, and improvement of VO2max after ID&BEET seems to be dependent on LDH activity, as well as on the serum concentration of MDA and β-carotene.

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“…The aim of this study was to evaluate the effect of regular physical activity on the intramuscular metabolic changes resulting from an I/R protocol in SCD mice. We paid particular attention to the abnormalities involved in the pathophysiology of the disease, such as intracellular acidosis (Chatel et al., ) and oxidative stress (Chirico & Pialoux, ; Nur et al., ). Overall, 7 weeks of endurance training did not reverse the exacerbated acidosis or the mitochondrial dysfunction or the muscular atrophy we previously reported (Chatel et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…Given that acidosis has been shown to have a strong involvement in RBC sickling and the resulting VOC (Chatel et al., ), it is tempting to speculate that any strategy that could reverse the I/R‐related exacerbation of intramuscular acidosis reported in SCD mice (Chatel et al., ) would be of great interest. We noticed previously that the severity of acidosis occurring after an acute electrostimulation protocol was reduced as a result of training (Chatel et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…Experimental Physiology c 2018 The Physiological Society muscle I/R protocol in a mouse model of SCD, we recently reported exacerbated metabolic changes, particularly high proton (H + ) and reactive oxygen species (ROS) accumulations, impaired mitochondrial function and altered muscle mass (Chatel et al, 2018c). These results are of great interest given that these abnormalities could worsen the repercussions of SCD (Chatel et al, 2018c;Chatel, Messonnier, & Bendahan, 2018b;Eltzschig & Eckle, 2011), constituting a vicious cycle (Chatel et al, 2018b;Verduzco & Nathan, 2009). On that basis, the metabolic repercussions of VOCs could be of interest to target as part of a therapeutic strategy aiming at the reversal or alleviation of these defects.…”

Section: Introductionmentioning

confidence: 99%

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Ischaemia‐induced muscle metabolic abnormalities are poorly alleviated by endurance training in a mouse model of sickle cell disease

Chatel

Messonnier

Vilmen

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?The aim of this study was to evaluate the potential beneficial effects of endurance training during an ischaemia–reperfusion protocol in a mouse model of sickle cell disease (SCD). What is the main finding and its importance?Endurance training did not reverse the metabolic defects induced by a simulated vaso‐occlusive crisis in SCD mice, with regard to intramuscular acidosis, mitochondrial dysfunction or anatomical properties. Our results suggest that endurance training would reduce the number of vaso‐occlusive crises rather than the complications related to vaso‐occlusive crises. Abstract The aim of this study was to investigate whether endurance training could limit the abnormalities described in a mouse model of sickle cell disease (SCD) in response to an ischaemia–reperfusion (I/R) protocol. Ten sedentary (HbSS‐SED) and nine endurance‐trained (HbSS‐END) SCD mice were submitted to a standardized protocol of I/R of the leg, during which ATP, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured using magnetic resonance spectroscopy. Forty‐eight hours later, skeletal muscles were harvested. Oxidative stress markers were then measured. Although the time course of protons accumulation was slightly different between trained and sedentary mice (P < 0.05), the extent of acidosis was similar at the end of the ischaemic period. The initial rate of phosphocreatine resynthesis measured at blood flow restoration, illustrating mitochondrial function, was not altered in trained mice compared with sedentary mice. Although several oxidative stress markers were not different between groups (P > 0.05), the I/R‐related increase of uric acid concentration observed in sedentary SCD mice (P < 0.05) was not present in the trained group. The spleen weight, generally used as a marker of the severity of the disease, was not different between groups (P > 0.05). In conclusion, endurance training did not limit the metabolic consequences of an I/R protocol in skeletal muscle of SCD mice, suggesting that the reduction in the severity of the disease previously demonstrated in the basal state would be attributable to a reduction of the occurrence of vaso‐occlusive crises rather than a decrease of the deleterious effects of vaso‐occlusive crises.

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Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease?

Cited by 14 publications

References 76 publications

Muscle structural, energetic and functional benefits of endurance exercise training in sickle cell disease

Muscle structural, energetic and functional benefits of endurance exercise training in sickle cell disease

Changes in Oxidative Stress, Inflammation, and Muscle Damage Markers Following Diet and Beetroot Juice Supplementation in Elite Fencers

Ischaemia‐induced muscle metabolic abnormalities are poorly alleviated by endurance training in a mouse model of sickle cell disease

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