Background: Despite the fact that patients with obstructive sleep apnoea syndrome (OSAS) often have symptoms at the level of skeletal muscle such as fatigue, the question of whether the structural, cellular and functional properties of limb skeletal muscles are affected has not been fully examined. Objective: The aim was to examine physiological and muscular parameters in patients with OSAS and to assess the relationship between these parameters and the clinical symptoms. Method: Eighteen patients with OSAS and 16 controls participated. Aerobic capacity was assessed using a submaximal test. Fibre type distribution and fibre area were analyzed on muscle biopsies taken from the tibialis anterior. The microvascularization was assessed using the following parameters: (1) the number of capillaries per fibre (CAF), (2) CAF per fibre area (CAFA), (3) capillary to fibre perimeter exchange (CFPE) index, which represents the interface between muscle fibre and capillaries, and (4) length of capillary/perimeter of the fibre (LC/PF) index or capillary tortuosity, which represents the percent of muscle fibre perimeter in contact with the wall of the microvessel. Results: The OSAS group had significantly lower predicted relative maximal oxygen uptake (p = 0.0047) which was inversely correlated to the apnoea/hypopnoea index (AHI; r = –0.6, p = 0.017). There was a significantly higher CFPE index for slow type I fibres (p = 0.007) and fast type II fibres (p = 0.0126) and a significantly higher LC/PF index for type I fibres (p = 0.0003) and type II fibres (p = 0.0285) in OSAS patients compared to controls. Conclusion: OSAS patients have a higher muscle microvascularization and a lower aerobic capacity than controls. Furthermore the aerobic capacity was inversely correlated to AHI.

Keywords:
Obstructive sleep apnoea syndrome, Capillary, Microvessel, Hypoxia, Oxygen uptake
1.
McNicholas WT, Ryan S: Obstructive sleep apnoea syndrome: translating science to clinical practice. Respirology 2006;11:136–144.
2.
Tarasiuk A, Greenberg-Dotan S, Brin YS, Simon T, Tal A, Reuveni H: Determinants affecting health-care utilization in obstructive sleep apnea syndrome patients. Chest 2005;128:1310–1314.
3.
Chervin RD: Sleepiness, fatigue, tiredness, and lack of energy in obstructive sleep apnea. Chest 2000;118:372–379.
4.
Aguillard RN: Daytime functioning in obstructive sleep apnea patients: exercise tolerance, subjective fatigue and sleepiness. Appl Psychophysiol Biofeedback 1998;23:207–217.
5.
Flück M: Functional, structural and molecular plasticity of mammalian skeletal muscle in response to exercise stimuli. J Exp Biol 2006;209:2239–2248.
6.
Andersen JL, Terzis G, Kryger A: Increase in the degree of coexpression of myosin heavy chain isoforms in skeletal muscle fibers of the very old. Muscle Nerve 1999;22:449–454.
7.
Kadi F: Adaptation of human skeletal muscle to training and anabolic steroids. Acta Physiol Scand Suppl 2000;646:1–52.
8.
Ferrara N, Gerber HP, LeCouter J: The biology of VEGF and its receptors. Nat Med 2003;9:669–676.
9.
Gustafsson T: Exercise and Angiogenic Growth Factors in Human Skeletal Muscle. Stockholm, Karolinska Institutet, 2005.
10.
Hansen J, Sander M, Hald CF, Victor RG, Thomas GD: Metabolic modulation of sympathetic vasoconstriction in human skeletal muscle: role of tissue hypoxia. J Physiol 2000;1:387–396.
11.
Hoppeler H, Vogt M: Muscle tissue adaptations to hypoxia. J Exp Biol 2001;204:3133–3139.
12.
Carrera M, Barbé F, Sauleda J, Tomás M, Gómez C, Agustí AG: Patients with obstructive sleep apnea exhibit genioglossus dysfunction that is normalized after treatment with continuous positive airway pressure. Am J Respir Crit Care Med 1999;159:1960–1966.
13.
Ferini-Strambi LJ, Smirne S, Moz U, Sferrazza B, Iannaccone S: Muscle fibre type and obstructive sleep apnea. Sleep Res Online 1998;1:24–27.
14.
Smirne S, Iannaccone S, Ferini-Strambi L, Comola M, Colombo E, Nemni R: Muscle fibre type and habitual snoring. Lancet 1991;337:597–599.
15.
Svanborg E: Impact of obstructive apnea syndrome on upper airway respiratory muscles. Respir Physiol Neurobiol 2005;28:263–272.
16.
Sauleda J, Garcia-Palmer FJ, Tarraga S, Maimo A, Palou A, Agusti AG: Skeletal muscle changes in patients with obstructive sleep apnoea syndrome. Respir Med 2003;97:804–810.
17.
Lindberg E, Gislason T: Epidemiology of sleep-related obstructive breathing. Sleep Med Rev 2000;4:411–433.
18.
Verin E, Tardif C, Pasquis P: Prevalence of daytime hypercapnia or hypoxia in patients with OSAS and normal lung function. Respir Med 2001;95:693–696.
19.
White DP: The pathogenesis of obstructive sleep apnea: advances in the past 100 years. Am J Respir Cell Mol Biol 2006;34:1–6.
20.
Guideline fifteen: guidelines for polygraphic assessment of sleep-related disorder (polysomnography). American Electroencephalografic Society. J Clin Neurophysiol 1994;11:116–124.
21.
Douglas NJ, Thomas S, Jan MA: Clinical value of polysomnography. Lancet 1992;339:347–350.
22.
Dingli K, Coleman EL, Vennelle M, Finch S, Wraith PK, Mackay TW, Douglas NJ: Evaluation of a portable device for diagnosing the sleep apnoea/hypopnoea syndrome. Eur Respir J 2003;21:253–259.
23.
Nunez R, Rey de Castro J, Socarras E CJ, Rubio R, Aizpuru F, Duran-Cantolla J: Validation study of a polygraphic screening device (BREAS SC20) in the diagnosis of sleep apnea-hypopnea syndrome. Arch Bronconeumol 2003;39:527–543.
24.
Engström LM, Ekblom B, Forsberg A, Seger J: Lifestyle – Function – Health. Ödeshög, Danagårds, 1993.
25.
Wilmore JH, Costill DL: Physiology of Sport and Exercise. Champaign, Human Kinetics, 2004.
26.
Åstrand PO, Rodahl K: Textbook of Work Physiology, Physiological Bases of Exercise. New York, McGraw-Hill Book Company, 1986.
27.
Henriksson KG: ‘Semi-open’ muscle biopsy technique. A simple outpatient procedure. Acta Neurol Scand 1979;59:317–323.
28.
Louwerens JW, van Linge B, de Klerk LW, Mulder PG, Snijders CJ: Peroneus longus and tibialis anterior muscle activity in the stance phase. A quantified electromyographic study of 10 controls and 25 patients with chronic ankle instability. Acta Orthop Scand 1995;66:517–523.
29.
Kadi F, Hägg G, Håkansson R, Holmner S, Butler-Brone GS, Thornell LE: Structural changes in male trapezuis muscle with work-related myalgia. Acta Neuropathol 1998;95:352–360.
30.
Kadi F, Charifi N, Denis C, Lexell J: Satellite cells and myonuclei in young and elderly women and men. Muscle Nerve 2004;29:120–127.
31.
Kadi F, Johansson F, Johansson R, Sjöström M, Henriksson J: Effects of one bout of endurance exercise on the expression of myogenin in human quadriceps muscle. Histochem Cell Biol 2004;121:329–334.
32.
Porter MM, Stuart S, Boij M, Lexell J: Capillary supply of the tibialis anterior muscle in young, healthy, and moderately active men and women. J Appl Physiol 2002;92:1451–1457.
33.
Charifi N, Kadi F, Feasson L, Costes F, Geyssant A, Denis C: Enhancement of microvessel tortuosity in the vastus lateralis muscle of old men in response to endurance training. J Physiol (Lond) 2003;554:559–569.
34.
Hepple RT, Mathieu-Costello O: Estimating the size of the capillary-to-fiber interface in skeletal muscle: a comparison of methods. J Appl Physiol 2001;91:2150–2156.
35.
Gustafsson T, Puntschart A, Kaijser L, Jansson E, Sundberg CJ: Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle. Am J Physiol 1999;276:H679–H685.
36.
Bloor CM: Angiogenesis during exercise and training. Angiogenesis 2005;8:263–271.
37.
Klagsbrun M, D’Amore PA: Vascular endothelial growth factor and its receptors. Cytokine Growth Factor Rev 1996;7:259–270.
38.
Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL: Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 1996;16:4604–4613.
39.
Tatsumi K, Kasahara Y, Kurosu K, Tanabe N, Takiguchi Y, Kuriyama T: Sleep oxygen desaturation and circulating leptin in obstructive sleep apnea-hypopnea syndrome. Chest 2005;127:716–721.
40.
Unal M, Ozturk L, Kanik A: The role of oxygen saturation measurement and body mass index in distinguishing between non-apnoeic snorers and patients with obstructive sleep apnoea syndrome. Clin Otolaryngol Allied Sci 2002;27:344–346.
41.
Gozal D, Lipton AJ, Jones KL: Circulating vascular endothelial growth factor levels in patients with obstructive sleep apnea. Sleep 2002;1:59–65.
42.
Imagawa S, Yamaguchi Y, Higuchi M, Neichi T, Hasegawa Y, Mukai HY, Suzuki N, Yamamoto M, Nagasawa T: Levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea-hypopnea syndrome. Blood 2002;1:393–394.
43.
Peled N, Shitrit D, Bendayan D, Peled E, Kramer MR: Association of elevated levels of vascular endothelial growth factor in obstructive sleep apnea syndrome with patient age rather than with obstructive sleep apnea syndrome severity. Respiration 2007;74:50–55.
44.
Deveci D, Marshall JM, Egginton S: Chronic hypoxia induces prolonged angiogenesis in skeletal muscles of rat. Exp Physiol 2002;87:287–291.
45.
Deveci D, Marshall JM, Egginton S: Relationship between capillary angiogenesis, fiber type, and fiber size in chronic systemic hypoxia. Am J Physiol Heart Circ Physiol 2001;281:H241–H252.
46.
Poole DC, Mathieu-Costello O: Effects of hypoxia on capillary orientation in anterior tibialis muscle of highly active mice. Respir Physiol 1990;82:1–10.
47.
Poole DC, Mathieu-Costello O: Skeletal muscle capillary geometry: adaptation to chronic hypoxia. Respir Physiol 1989;77:21–29.
48.
Lundby C, Pilegaard H, Andersen JL, van Hall G, Sander M, Calbet JA: Acclimatization to 4,100 m does not change capillary density or mRNA expression of potential angiogenesis regulatory factors in human skeletal muscle. J Exp Biol 2004;207:3865–3871.
49.
Piehl Aulin K, Svedenhag J, Wide L, Berglund B, Saltin B: Short-term intermittent normobaric hypoxia – haematological, physiological and mental effects. Scand J Med Sci Sports 1998;8:132–137.
50.
Tuomisto TT, Rissanen TT, Vajanto I, Korkeela A, Rutanen J, Yla-Herttuala S: HIF-VEGF-VEGFR-2, TNF-alpha and IGF pathways are upregulated in critical human skeletal muscle ischemia as studied with DNA array. Atherosclerosis 2004;174:111–120.
51.
Gavin TP, Stallings HW 3rd, Zwetsloot KA, Westerkamp LM, Ryan NA, Moore RA, Pofahl WE, Hickner RC: Lower capillary density but no difference in VEGF expression in obese vs. lean young skeletal muscle in humans. J Appl Physiol 2005;98:315–321.
52.
Kadi F, Thornell LE: Training affects myosin heavy chain phenotype in the trapezius muscle of women. Histochem Cell Biol 1999;112:73–78.
53.
Staron RS, Leonardi MJ, Karapondo DL, Malicky ES, Falkel JE, Hagerman FC, Hikida RS: Strength and skeletal muscle adaptations in heavy-resistance-trained women after detraining and retraining. J Appl Physiol 1991;70:631–640.
54.
Giebelhaus V, Strohl KP, Lormes W, Lehmann M, Netzer N: Physical exercise as an adjunct therapy in sleep apnea – an open trial. Sleep Breath 2000;4:173–176.
55.
Norman JF, Von Essen S, Fuchs RH, McElligott M: Exercise training effect on obstructive sleep apnea syndrome. Sleep Res Online 2000;3:121–129.
© 2008 S. Karger AG, Basel
2008
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.