Noninvasive optical characterization of muscle blood flow, oxygenation, and metabolism in women with fibromyalgia

Yu Shang, Katelyn Gurley, Brock Symons, Douglas Long, Ratchakrit Srikuea, Leslie J Crofford, Charlotte A Peterson, Guoqiang Yu, Yu Shang, Katelyn Gurley, Brock Symons, Douglas Long, Ratchakrit Srikuea, Leslie J Crofford, Charlotte A Peterson, Guoqiang Yu

Abstract

Introduction: Women with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM.

Methods: Fourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily increasing from 20 to 70% maximal voluntary isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy-hemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO2), were continuously monitored throughout protocols using a custom-built hybrid diffuse optical instrument that combined a commercial near-infrared oximeter for tissue oxygenation measurements and a custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2) were calculated from the measured blood flow and oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion) recovery in muscle hemodynamics was characterized by the recovery half-time, a time interval from the end of manipulation to the time that tissue hemodynamics reached a half-maximal value.

Results: Subjects with FM had similar hemodynamic and metabolic response/recovery patterns as healthy controls during exercise and during arterial occlusion. However, tissue rOEF during exercise in subjects with FM was significantly lower than in healthy controls, and the half-times of oxygenation recovery (Δ[HbO2] and Δ[Hb]) were significantly longer following fatiguing exercise and cuff occlusion.

Conclusions: Our results suggest an alteration of muscle oxygen utilization in the FM population. This study demonstrates the potential of using combined diffuse optical spectroscopies (i.e., NIRS/DCS) to comprehensively evaluate tissue oxygen and flow kinetics in skeletal muscle.

Figures

Figure 1
Figure 1
Illustrative thigh muscle oxygenation responses throughout fatiguing exercise in (a) a subject with fibromyalgia (FM) and (b) a healthy control. The oxygenation responses include oxy- and deoxyhemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC) and oxygen saturation (StO2), all presented in absolute values. The first two vertical lines indicate the beginning and the end of fatiguing exercise respectively, and the last four vertical lines indicate the time points 3, 6, 9 and 12 minutes after exercise. The arrow indicates the time points immediately post-exercise (over 6 seconds). Note that the muscle motion artifacts during exercise and during maximal voluntary isometric contraction (MVIC) tests at time points 3, 6, 9 and 12 minute post-exercise may contaminate optical measurements, as seen from the peaks in the figure.
Figure 2
Figure 2
Illustrative relative blood flow (rBF), oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2) throughout fatiguing exercise in (a) a subject with firbromyalgia (FM) and (b) a healthy control, all presented in percentage relative to baseline (%). The first two vertical lines indicate the beginning and the end of fatiguing exercise respectively, and the last four vertical lines indicate the time points 3, 6, 9 and 12 minutes after exercise. The arrow indicates the time points immediately post-exercise (over 6 seconds). Note that the muscle motion artifacts during exercise and during maximal voluntary isometric contraction (MVIC) tests at time points 3, 6, 9 and 12 minute post-exercise may contaminate optical measurements, as seen from the peaks in the figure.
Figure 3
Figure 3
Six-second average data immediately after fatiguing exercise (see the arrows in Figure 1 and Figure 2) as a measure of exercise-induced hemodynamic responses. All parameters were normalized/divided to their baselines (%), resulting in relative change of oxy- and deoxyhemoglobin concentration(r[HbO2] and r[Hb]), total hemoglobin concentration (rTHC), oxygen saturation (rStO2), blood flow (rBF), oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2). The Student's t-test was used to compare the average rBF (nHC = 23, nFM = 14), r[HbO2], r[Hb], rTHC, rStO2, rOEF and rVO2 (nHC = 20, nFM = 12) in subjects with fibromyalgia (FM) and healthy controls (HC) immediately after fatiguing exercise. *P < 0.05.
Figure 4
Figure 4
Illustrative recovery half-times of relative blood flow (rBF), change in oxyhemoglobin concentration (Δ[HbO2]) and change in deoxyhemoglobin concentration (Δ[Hb]) following fatiguing exercise in (a) a subject with fibromyalgia (FM) and (b) a healthy control. The vertical solid lines indicate the ending of exercise. The horizontal dashed and dotted lines indicate the maximal and half-maximal recovery values of hemodynamic variables, respectively. The vertical dotted lines indicate the recovery half-times.
Figure 5
Figure 5
Average recovery half-times of relative blood flow (rBF) (nHC = 23, nFM = 14), change in oxyhemoglobin concentration (Δ[HbO2]) and change in deoxyhemoglobin concentration (Δ[Hb]) (nHC = 20, nFM = 12) in subjects with fibromyalgia (FM) and healthy controls (HC) following fatiguing exercise. The Student's t-test was used to compare the half-times between FM and healthy subjects. *P < 0.05.
Figure 6
Figure 6
Illustrative recovery half-times of relative blood flow (rBF), change in oxyhemoglobin concentration (Δ[HbO2]) and change in deoxyhemoglobin concentration (Δ[Hb]) following arm cuff occlusion in (a) a subject with fibromyalgia (FM) and (b) a healthy control. The two solid vertical lines indicate the beginning and ending of cuff occlusion. The horizontal dashed and dotted lines indicate the maximal and half-maximal recovery values of hemodynamic variables, respectively. The vertical dotted lines indicate the recovery half-times.
Figure 7
Figure 7
Average recovery half-times of relative blood flow (rBF) (nHC = 23, nFM = 14), change in oxyhemoglobin concentration (Δ[HbO2]) and change in deoxyhemoglobin concentration (Δ[Hb]) (nHC = 20, nFM = 12) in subjects with fibromyalgia (FM) and healthy controls (HC) following arm cuff occlusion. The Student's t-test was used to compare the half-times between FM and healthy subjects. *P < 0.05; **P < 0.005.

References

    1. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995;14:19–28. doi: 10.1002/art.1780380104.
    1. Yunus MB. Gender differences in fibromyalgia and other related syndromes. J Gend Specif Med. 2002;14:42–47.
    1. Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002;14:528–538. doi: 10.1002/cncr.10245.
    1. Yildiz S, Kiralp MZ, Akin A, Keskin I, Ay H, Dursun H, Cimsit M. A new treatment modality for fibromyalgia syndrome: Hyperbaric oxygen therapy. J Int Med Res. 2004;14:263–267.
    1. McCully KK, Smith S, Rajaei S, Leigh JS, Natelson BH. Blood flow and muscle metabolism in chronic fatigue syndrome. Clin Sci. 2003;14:641–647. doi: 10.1042/CS20020279.
    1. Cordero MD, De Miguel M, Fernandez AMM, Lopez IMC, Maraver JG, Cotan D, Izquierdo LG, Bonal P, Campa F, Bullon P, Navas P, Alcazar JAS. Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease. Arthritis Res Ther. 2010;14:R17. doi: 10.1186/ar2918.
    1. Lindh M, Johansson G, Hedberg M, Henning GB, Grimby G. Muscle-fiber characteristics, capillaries and enzymes in patients with fibromyalgia and controls. Scand J Rheumatol. 1995;14:34–37. doi: 10.3109/03009749509095152.
    1. Morf S, Amann-Vesti B, Forster A, Franzeck UK, Koppensteiner R, Uebelhart D, Sprott H. Microcirculation abnormalities in patients with fibromyalgia - measured by capillary microscopy and laser fluxmetry. Arthritis Res Ther. 2005;14:R209–R216. doi: 10.1186/ar1459.
    1. Grassi W, Core P, Carlino G, Salaffi F, Cervini C. Capillary-Permeability in Fibromyalgia. J Rheumatol. 1994;14:1328–1331.
    1. Kasikcioglu E, Dinler M, Berker E. Reduced tolerance of exercise in fibromyalgia may be a consequence of impaired microcirculation initiated by deficient action of nitric oxide. Med Hypotheses. 2006;14:950–952. doi: 10.1016/j.mehy.2005.11.028.
    1. McIver KL, Evans C, Kraus RM, Ispas L, Sciotti VM, Hickner RC. NO-mediated alterations in skeletal muscle nutritive blood flow and lactate metabolism in fibromyalgia. Pain. 2006;14:161–169. doi: 10.1016/j.pain.2005.10.032.
    1. Klemp P, Staberg B, Korsgard J, Nielsen HV, Crone P. Reduced blood-flow in fibromyotic muscles during ultrasound therapy. Scand J Rehabil Med. 1983;14:21–23.
    1. Meiworm L, Jakob E, Walker UA, Peter HH, Keul J. Patients with fibromyalgia benefit from aerobic endurance exercise. Clin Rheumatol. 2000;14:253–257. doi: 10.1007/s100670070040.
    1. Park JH, Phothimat P, Oates CT, Hernanz-Schulman M, Olsen NJ. Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia. Arthritis Rheum. 1998;14:406–413. doi: 10.1002/1529-0131(199803)41:3<406::AID-ART5>;2-L.
    1. Jeschonneck M, Grohmann G, Hein G, Sprott H. Abnormal microcirculation and temperature in skin above tender points in patients with fibromyalgia. Rheumatology. 2000;14:917–921. doi: 10.1093/rheumatology/39.8.917.
    1. Klemp P, Nielsen HV, Korsgard J, Crone P. Blood-Flow in Fibromyotic Muscles. Scand J Rehabil Med. 1982;14:81–82.
    1. Elvin A, Sioteen AK, Nilsson A, Kosek E. Decreased muscle blood flow in fibromyalgia patients during standardised muscle exercise: A contrast media enhanced colour doppler study. Eur J Pain. 2006;14:137–144. doi: 10.1016/j.ejpain.2005.02.001.
    1. Dinler M, Kasikcioglu E, Akin A, Sayli O, Aksoy C, Oncel A, Berker E. Exercise capacity and oxygen recovery half times of skeletal muscle in patients with fibromyalgia. Rheumatol Int. 2007;14:311–313.
    1. Dinler M, Diracoglu D, Kasikcioglu E, Sayli O, Akin A, Aksoy C, Oncel A, Berker E. Effect of aerobic exercise training on oxygen uptake and kinetics in patients with fibromyalgia. Rheumatol Int. 2009;14:281–284. doi: 10.1007/s00296-009-1126-x.
    1. Bennett RM, Clark SR, Goldberg L, Nelson D, Bonafede RP, Porter J, Specht D. Aerobic Fitness in Patients with Fibrositis - a Controlled-Study of Respiratory Gas-Exchange and Xe-133 Clearance from Exercising Muscle. Arthritis Rheum. 1989;14:454–460. doi: 10.1002/anr.1780320415.
    1. Strobel ES, Krapf M, Suckfull M, Bruckle W, Fleckenstein W, Muller W. Tissue oxygen measurement and P-31 magnetic resonance spectroscopy in patients with muscle tension and fibromyalgia. Rheumatol Int. 1997;14:175–180. doi: 10.1007/BF01330292.
    1. Sako T, Hamaoka T, Higuchi H, Kurosawa Y, Katsumura T. Validity of NIR spectroscopy for quantitatively measuring muscle oxidative metabolic rate in exercise. J Appl Physiol. 2001;14:338–344.
    1. Shang Y, Zhao Y, Cheng R, Dong L, Irwin D, Yu G. Portable optical tissue flow oximeter based on diffuse correlation spectroscopy. Opt Lett. 2009;14:3556–3558. doi: 10.1364/OL.34.003556.
    1. Ferrari M, Muthalib M, Quaresima V. The use of near-infrared spectroscopy in understanding skeletal muscle physiology: recent developments. Philos Transact A Math Phys Eng Sci. 2011;14:4577–4590. doi: 10.1098/rsta.2011.0230.
    1. McCully KK, Smith S, Rajaei S, Leigh JS, Natelson BH. Muscle metabolism with blood flow restriction in chronic fatigue syndrome. J Appl Physiol. 2004;14:871–878.
    1. Shang Y, Symons TB, Durduran T, Yodh AG, Yu G. Effects of muscle fiber motion on diffuse correlation spectroscopy blood flow measurements during exercise. Biomed Opt Express. 2010;14:500–511. doi: 10.1364/BOE.1.000500.
    1. Yu G, Durduran T, Lech G, Zhou C, Chance B, Mohler ER, Yodh AG. Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies. J Biomed Opt. 2005;14:024027. doi: 10.1117/1.1884603.
    1. Yu G, Shang Y, Zhao Y, Cheng R, Dong L, Saha SP. Intraoperative evaluation of revascularization effect on ischemic muscle hemodynamics using near-infrared diffuse optical spectroscopies. J Biomed Opt. 2011;14:027004. doi: 10.1117/1.3533320.
    1. Dietsche G, Ninck M, Ortolf C, Li J, Jaillon F, Gisler T. Fiber-based multispeckle detection for time-resolved diffusing-wave spectroscopy: characterization and application to blood flow detection in deep tissue. Appl Opt. 2007;14:8506–8514. doi: 10.1364/AO.46.008506.
    1. Durduran T, Yu G, Burnett MG, Detre JA, Greenberg JH, Wang JJ, Zhou C, Yodh AG. Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation. Opt Lett. 2004;14:1766–1768. doi: 10.1364/OL.29.001766.
    1. Li J, Dietsche G, Iftime D, Skipetrov SE, Maret G, Elbert T, Rockstroh B, Gisler T. Noninvasive detection of functional brain activity with near-infrared diffusing-wave spectroscopy. J Biomed Opt. 2005;14:44002. doi: 10.1117/1.2007987.
    1. Durduran T. PhD thesis. University of Pennsylvania, Department of Physics and Astronomy; 2004. Non-Invasive measurements of tissue hemodynamics with hybrid diffuse optical methods.
    1. Shang Y, Chen L, Toborek M, Yu G. Diffuse optical monitoring of repeated cerebral ischemia in mice. Opt Express. 2011;14:20301–20315. doi: 10.1364/OE.19.020301.
    1. Kim MN, Durduran T, Frangos S, Edlow BL, Buckley EM, Moss HE, Zhou C, Yu G, Choe R, Maloney-Wilensky E, Maloney-Wilensky E, Wolf RL, Grady MS, Greenberg JH, Levine JM, Yodh AG, Detre JA, Kofke WA. Noninvasive measurement of cerebral blood flow and blood oxygenation using near-infrared and diffuse correlation spectroscopies in critically brain-injured adults. Neurocrit Care. 2010;14:173–180. doi: 10.1007/s12028-009-9305-x.
    1. Zhou C, Eucker SA, Durduran T, Yu G, Ralston J, Friess SH, Ichord RN, Margulies SS, Yodh AG. Diffuse optical monitoring of hemodynamic changes in piglet brain with closed head injury. J Biomed Opt. 2009;14:034015. doi: 10.1117/1.3146814.
    1. Yu G, Floyd TF, Durduran T, Zhou C, Wang JJ, Detre JA, Yodh AG. Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI. Opt Express. 2007;14:1064–1075. doi: 10.1364/OE.15.001064.
    1. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Fam AG, Farber SJ, Fiechtner JJ, Franklin CM, Gatter RA, Hamaty D, Lessard J, Lichtbroun AS, Masi AT, Mccain GA, Reynolds WJ, Romano TJ, Russell IJ, Sheon RP. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;14:160–172. doi: 10.1002/art.1780330203.
    1. Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;14:1381–1395. doi: 10.1249/01.MSS.0000078924.61453.FB.
    1. Roos MR, Rice CL, Connelly DM, Vandervoort AA. Quadriceps muscle strength, contractile properties, and motor unit firing rates in young and old men. Muscle Nerve. 1999;14:1094–1103. doi: 10.1002/(SICI)1097-4598(199908)22:8<1094::AID-MUS14>;2-G.
    1. KentBraun JA, leBlanc R. Quantitation of central activation failure during maximal voluntary contractions in humans. Muscle Nerve. 1996;14:861–869. doi: 10.1002/(SICI)1097-4598(199607)19:7<861::AID-MUS8>;2-7.
    1. Wolfe F. Fatigue assessments in rheumatoid arthritis: Comparative performance of visual analog scales and longer fatigue questionnaires in 7760 patients. J Rheumatol. 2004;14:1896–1902.
    1. Altan L, Bingol U, Aykac M, Koc Z, Yurtkuran M. Investigation of the effects of pool-based exercise on fibromyalgia syndrome. Rheumatol Int. 2004;14:272–277.
    1. Munk N, Symons B, Shang Y, Cheng R, Yu G. Noninvasively measuring the hemodynamic effects of massage on skeletal muscle: A novel hybrid near-infrared diffuse optical instrument. J Bodyw Mov Ther. 2012;14:22–28. doi: 10.1016/j.jbmt.2011.01.018.
    1. Fantini S, Franceschinifantini MA, Maier JS, Walker SA, Barbieri B, Gratton E. Frequency-Domain Multichannel Optical-Detector for Noninvasive Tissue Spectroscopy and Oximetry. Optical Engineering. 1995;14:32–42. doi: 10.1117/12.183988.
    1. Strangman G, Franceschini MA, Boas DA. Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters. Neuroimage. 2003;14:865–879. doi: 10.1016/S1053-8119(03)00021-1.
    1. Arnold JMO, Ribeiro JP, Colucci WS. Muscle blood-flow during forearm exercise in patients with severe heart-failure. Circulation. 1990;14:465–472. doi: 10.1161/01.CIR.82.2.465.
    1. Wiener DH, Fink LI, Maris J, Jones RA, Chance B, Wilson JR. Abnormal skeletal-muscle bioenergetics during exercise in patients with heart-failure - role of reduced muscle blood-flow. Circulation. 1986;14:1127–1136. doi: 10.1161/01.CIR.73.6.1127.
    1. Chance B, Dait MT, Zhang CD, Hamaoka T, Hagerman F. Recovery from exercise-induced desaturation in the quadriceps muscles of elite competitive rowers. Am J Physiol. 1992;14:C766–C775.
    1. Wang B, Tian Q, Zhang Z, Gong H. Comparisons of local and systemic aerobic fitness parameters between finswimmers with different athlete grade levels. Eur J Appl Physiol. 2012;14:567–578. doi: 10.1007/s00421-011-2007-z.
    1. Yano T, Yunoki T, Matsuura R, Arimitsu T, Kimura T. Excessive oxygen uptake during exercise and recovery in heavy exercise. Physiol Res. 2007;14:721–725.
    1. Valkeinen H, Hakkinen A, Hannonen P, Hakkinen K, Alen M. Acute heavy-resistance exercise-induced pain and neuromuscular fatigue in elderly women with fibromyalgia and in healthy controls - Effects of strength training. Arthritis Rheum. 2006;14:1334–1339. doi: 10.1002/art.21751.
    1. Valkeinen H, Alen M, Hakkinen A, Hannonen P, Kukkonen-Harjula K, Hakkinen K. Effects of concurrent strength and endurance training on physical fitness and symptoms in postmenopausal women with fibromyalgia: A randomized controlled trial. Arch Phys Med Rehabil. 2008;14:1660–1666. doi: 10.1016/j.apmr.2008.01.022.
    1. Robergs RA, Ghiasvand F, Parker D. Biochemistry of exercise-induced metabolic acidosis. American Journal of Physiology-Regulatory Integrative and Comparative Physiology. 2004;14:R502–R516. doi: 10.1152/ajpregu.00114.2004.
    1. Harris K, Walker PM, Mickle DAG, Harding R, Gatley R, Wilson GJ, Kuzon B, Mckee N, Romaschin AD. Metabolic response of skeletal-muscle to ischemia. Am J Physiol Regul Integr Comp Physiol. 1986;14:H213–H220.
    1. Katz DL, Greene L, Ali A, Faridi Z. The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation. Med Hypoth. 2007;14:517–525. doi: 10.1016/j.mehy.2005.10.037.
    1. Leal ECP, Lopes-Martins RAB, Vanin AA, Baroni BM, Grosselli D, De Marchi T, Iversen VV, Bjordal JM. Effect of 830 nm low-level laser therapy in exercise-induced skeletal muscle fatigue in humans. Lasers Med Sci. 2009;14:425–431. doi: 10.1007/s10103-008-0592-9.
    1. McGuire BJ, Secomb TW. Estimation of capillary density in human skeletal muscle based on maximal oxygen consumption rates. Am J Physiol-Heart Circul Physiol. 2003;14:H2382–H2391.
    1. Robbins JL, Jones WS, Duscha BD, Allen JD, Kraus WE, Regensteiner JG, Hiatt WR, Annex BH. Relationship between leg muscle capillary density and peak hyperemic blood flow with endurance capacity in peripheral artery disease. J Appl Physiol. 2011;14:81–86. doi: 10.1152/japplphysiol.00141.2011.
    1. Gurley K, Shang Y, Yu G. Noninvasive optical quantification of absolute blood flow, blood oxygenation, and oxygen consumption rate in exercising skeletal muscle. J Biomed Opt. 2012;14:075010. doi: 10.1117/1.JBO.17.7.075010.

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