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

Angèle N Merlet, Léonard Féasson, Pablo Bartolucci, Christophe Hourdé, Céline Schwalm, Barnabas Gellen, Frédéric Galactéros, Louise Deldicque, Marc Francaux, Laurent A Messonnier, EXDRE Collaborative Study Group, Angèle N Merlet, Léonard Féasson, Pablo Bartolucci, Christophe Hourdé, Céline Schwalm, Barnabas Gellen, Frédéric Galactéros, Louise Deldicque, Marc Francaux, Laurent A Messonnier, EXDRE Collaborative Study Group

Abstract

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 moderate-intensity 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.

© 2020 Wiley Periodicals LLC.

References

REFERENCES

    1. Piel FB, Steinberg MH, Rees DC. Sickle cell disease. N Engl J Med. 2017;377(3):305.
    1. Gladwin MT, Sachdev V. Cardiovascular abnormalities in sickle cell disease. J Am Coll Cardiol. 2012;59(13):1123-1133.
    1. Quinn CT, Sargent JW. Daytime steady-state haemoglobin desaturation is a risk factor for overt stroke in children with sickle cell anaemia. Br J Haematol. 2008;140(3):336-339.
    1. Setty BN, Stuart MJ, Dampier C, Brodecki D, Allen JL. Hypoxaemia in sickle cell disease: biomarker modulation and relevance to pathophysiology. Lancet. 2003;362(9394):1450-1455.
    1. Ferguson SK, Harral JW, Pak DI, et al. Impact of cell-free hemoglobin on contracting skeletal muscle microvascular oxygen pressure dynamics. Nitric Oxide. 2018;76:29-36.
    1. Ravelojaona M, Féasson L, Oyono-Enguéllé S, et al. Evidence for a profound remodeling of skeletal muscle and its microvasculature in sickle cell anemia. Am J Pathol. 2015;185(5):1448-1456.
    1. Nahavandi M, Tavakkoli F, Hasan SP, Wyche MQ, Castro O. Cerebral oximetry in patients with sickle cell disease. Eur J Clin. Invest. 2004;34(2):143-148.
    1. Nahavandi M, Nichols JP, Hassan M, Gandjbakhche A, Kato GJ. Near-infrared spectra absorbance of blood from sickle cell patients and normal individuals. Hematology. 2009;14(1):46-48.
    1. Charlot K, Antoine-Jonville S, Moeckesch B, et al. Cerebral and muscle microvascular oxygenation in children with sickle cell disease: influence of hematology, hemorheology and vasomotion. Blood Cells Mol Dis. 2017;65:23-28.
    1. Brooks GA. The science and translation of lactate shuttle theory. Cell Metab. 2018;27(4):757-785.
    1. Miller GJ, Serjeant GR, Sivapragasam S, Petch MC. Cardio-pulmonary responses and gas exchange during exercise in adults with homozygous sickle-cell disease (sickle-cell anaemia). Clin Sci. 1973;44(2):113-128.
    1. Callahan LA, Woods KF, Mensah GA, Ramsey LT, Barbeau P, Gutin B. Cardiopulmonary responses to exercise in women with sickle cell anemia. Am J Respir Crit Care Med. 2002;165(9):1309-1316.
    1. Chatel B, Messonnier LA, Bendahan D. Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease? Exp Physiol. 2018;103(9):1213-1220.
    1. Jones EJ, Bishop PA, Woods AK, Green JM. Cross-sectional area and muscular strength: a brief review. Sports Med. 2008;38(12):987-994.
    1. Merlet AN, Chatel B, Hourdé C, et al. How sickle cell disease impairs skeletal muscle function: implications in daily life. Med Sci Sports Exerc. 2019;51(1):4-11.
    1. Messonnier L, Freund H, Féasson L, et al. Blood lactate exchange and removal abilities after relative high-intensity exercise: effects of training in normoxia and hypoxia. Eur J Appl Physiol. 2001;84(5):403-412.
    1. Messonnier L, Freund H, Denis C, Féasson L, Lacour JR. Effects of training on lactate kinetics parameters and their influence on short high-intensity exercise performance. Int J Sports Med. 2006;27(1):60-66.
    1. Bankolé LC, Millet GY, Temesi J, et al. Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy: A randomized controlled trial. Medicine (Baltimore). 2016;95(31):e4497.
    1. Maltais F, LeBlanc P, Simard C, et al. Skeletal muscle adaptation to endurance-exercise training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996;154(2 Pt 1):442-447.
    1. Juel C. Training-induced changes in membrane transport proteins of human skeletal muscle. Eur J Appl Physiol. 2006;96(6):627-635.
    1. Juel C. Lactate-proton cotransport in skeletal muscle. Physiol Rev. 1997;77(2):321-358.
    1. Chatel B, Bendahan D, Hourdé C, et al. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice. FASEB J. 2017;31(6):2562-2575.
    1. Liem RI, Akinosun M, Muntz DS, Thompson AA. Feasibility and safety of home exercise training in children with sickle cell anemia. Pediatr Blood Cancer. 2017;12:64.
    1. Gellen B, Messonnier LA, Galactéros F, et al. Moderate-intensity endurance-exercise training in sickle-cell disease patients without severe chronic complications: a randomized-controlled trial. Lancet Haematol. 2018;5(11):e554-e562.
    1. Messonnier LA, Gellen B, Lacroix R, et al. Physiological evaluation for endurance exercise prescription in sickle cell disease. Med Sci Sports Exerc. 2019;51(9):1795-1801.
    1. Henriksson KG. "Semi-open" muscle biopsy technique. A simple outpatient procedure. Acta Neurol Scand. 1979;59:317-323.
    1. Freund H, Lonsdorfer J, Oyono-Enguéllé S, Lonsdorfer A, Bogui P. Lactate exchange and removal abilities in sickle cell patients and in untrained and trained healthy humans. J Appl Physiol (1985). 1992;73(6):2580-2587.
    1. Osnes JB, Hermansen L. Acid-base balance after maximal exercise of short duration. J Appl Physiol. 1972;32(1):59-63.
    1. Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol. 1983;61(12):1444-1461.
    1. Messonnier LA, Emhoff CA, Fattor JA, Horning MA, Carlson TJ, Brooks GA. Lactate kinetics at the lactate threshold in trained and untrained men. J Appl Physiol. 2013;114(11):1593-1602.
    1. Beneke R, Hutler M, Von Duvillard SP, Sellens M, Leithauser RM. Effect of test interruptions on blood lactate during constant workload testing. Med Sci Sports Exerc. 2003;35(9):1626-1630.
    1. Anthi A, Machado RF, Jison ML, et al. Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertension. Am J Respir Crit Care Med. 2007;175:1272-1279.
    1. Ainsworth BE, Jacobs DR Jr, Leon AS. Validity and reliability of self-reported physical activity status: the Lipid Research Clinics questionnaire. Med Sci Sports Exerc. 1993;25(1):92-98.
    1. Ainsworth BE, Haskell WL, Herrmann SD, et al. 2011 Compendium of physical activities: a second update of codes and MET values. Med Sci Sports Exerc. 2011;43(8):1575-1581.
    1. Meunier B, Picard B, Astruc T, Labas R. Development of image analysis tool for the classification of muscle fibre type using immunohistochemical staining. Histochem Cell Biol. 2010;134(3):307-317.
    1. Sale DG. Influence of exercise and training on motor unit activation. Exerc Sport Sci Rev. 1987;15:95-151.
    1. Brierley EJ, Johnson MA, Lightowlers RN, James OF, Turnbull DM. Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle. Ann Neurol. 1998;43(2):217-223.
    1. Zierz CM, Joshi PR, Zierz S. Frequencies of myohistological mitochondrial changes in patients with mitochondrial DNA deletions and the common m.3243A>G point mutation. Neuropathology. 2015;35(2):130-136.
    1. Konokhova Y, Spendiff S, Jagoe RT, et al. Failed upregulation of TFAM protein and mitochondrial DNA in oxidatively deficient fibers of chronic obstructive pulmonary disease locomotor muscle. Skelet Muscle. 2016;6:10.
    1. Bua E, Johnson J, Herbst A, et al. Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. Am J Hum Genet. 2006;79(3):469-480.
    1. Greaves LC, Reeve AK, Taylor RW, Turnbull DM. Mitochondrial DNA and disease. J Pathol. 2012;226(2):274-286.
    1. Meinild Lundby AK, Jacobs RA, Gehrig S, et al. Exercise training increases skeletal muscle mitochondrial volume density by enlargement of existing mitochondria and not de novo biogenesis. Acta Physiol (Oxf). 2018;222(1). .
    1. Gan Z, Fu T, Kelly DP, Vega RB. Skeletal muscle mitochondrial remodeling in exercise and diseases. Cell Res. 2018;28(10):969-980.
    1. Gollnick PD. Metabolism of substrates: energy substrate metabolism during exercise and as modified by training. Fed Proc. 1985;44(2):353-357.
    1. Chatel B, Messonnier LA, Barge Q, et al. Endurance-exercise training reduces exercise-induced acidosis and improves muscle function in a mouse model of sickle cell disease. Mol Genet Metab. 2018;123(3):400-410.
    1. Juel C. Regulation of pH in human skeletal muscle: adaptations to physical activity. Acta Physiol (Oxf). 2008;193(1):17-24.
    1. Thomas C, Bishop DJ, Lambert K, Mercier J, Brooks GA. Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status. Am J Physiol Regul Integr Comp Physiol. 2012;302(1):R1-R14.
    1. Juel C, Klarskov C, Nielsen JJ, Krustrup P, Mohr M, Bangsbo J. Effect of high-intensity intermittent training on lactate and H+ release from human skeletal muscle. Am J Physiol Endocrinol Metab. 2004;286(2):E245-E251.
    1. Juel C, Holten MK, Dela F. Effects of strength training on muscle lactate release and MCT1 and MCT4 content in healthy and type 2 diabetic humans. J Physiol. 2004;556(Pt 1):297-304.
    1. Campbell A, Minniti CP, Nouraie M, et al. Prospective evaluation of haemoglobin oxygen saturation at rest and after exercise in paediatric sickle cell disease patients. Br J Haematol. 2009;147(3):352-359.
    1. Delclaux C, Zerah-Lancner F, Bachir D, et al. Factors associated with dyspnea in adult patients with sickle cell disease. Chest. 2005;128(5):3336-3344.
    1. Gladwin MT, Schechter AN, Ognibene FP, et al. Divergent nitric oxide bioavailability in men and women with sickle cell disease. Circulation. 2003;107(2):271-278.
    1. Nath KA, Katusic ZS, Gladwin MT. The perfusion paradox and vascular instability in sickle cell disease. Microcirculation. 2004;11(2):179-193.
    1. Hackney AC, Hezier W, Gulledge TP, et al. Effects of hydroxyurea administration on the body weight, body composition and exercise performance of patients with sickle-cell anaemia. Clin Sci (Lond). 1997;92(5):481-486.
    1. Merlet AN, Messonnier LA, Coudy-Gandilhon C, et al. Beneficial effects of endurance exercise training on skeletal muscle microvasculature in sickle cell disease patients. Blood. 2019;134(25):2233-2241.
    1. Pedersen BK, Saltin B. Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports. 2006;16(Suppl 1):3-63.
    1. Pedersen BK, Saltin B. Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports. 2015;25(Suppl 3):1-72.
    1. Melo HN, Stoots SJ, Pool MA, et al. Objectively measured physical activity levels and sedentary time in children and adolescents with sickle cell anemia. PLoS One. 2018;13(12):e0208916.
    1. Ogunsile FJ, Bediako SM, Nelson J, et al. Metabolic syndrome among adults living with sickle cell disease. Blood Cells Mol Dis. 2019;74:25-29.
    1. Woods KF, Ramsey LT, Callahan LA, et al. Body composition in women with sickle cell disease. Ethn Dis. 2001;11(1):30-35.
    1. Akinsheye I, Klings ES. Sickle cell anemia and vascular dysfunction: the nitric oxide connection. J Cell Physiol. 2010;224(3):620-625.
    1. Wood KC, Hsu LL, Gladwin MT. Sickle cell disease vasculopathy: a state of nitric oxide resistance. Free Radic Biol Med. 2008;44(8):1506-1528.
    1. Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta.Physiol. 2007;191(1):59-66.
    1. Bailey SJ, Fulford J, Vanhatalo A, et al. Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol (1985). 2010;109(1):135-148.
    1. Larsen FJ, Schiffer TA, Borniquel S, et al. Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab. 2011;13:149-159.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere