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

Disclosures

Arthritis Res Ther. 2012;14(6) 

In This Article

Abstract and Introduction

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.

Introduction

Fibromyalgia (FM) is a common chronic widespread pain syndrome affecting approximately 2 to 5% of the US population.[1,2] Historically, older women are more susceptible to FM compared to men or young women.[2–4] People suffering from FM have symptoms of increased muscle fatigue and reduced tolerance to exercise, similar to patients with chronic fatigue syndrome (CFS).[5] Although the specific pathogenic mechanisms of FM remain unclear, studies have suggested that the muscle pain and fatigue of FM may be associated with mitochondrial dysfunction,[6] lower capillary density,[7,8] reduced capillary permeability,[9] or impaired vasodilatory capacity.[10,11] Those impairments may consequently affect muscle tissue microcirculation and oxygen metabolism. However, previous studies investigating peripheral/muscle blood flow or oxygen consumption in populations with FM have reported conflicting results.[8,11–17] Some studies have found reduced skin/muscle blood flow or oxygen consumption in people with FM,[8,11,12,14,15,17] whereas others reported that muscle blood flow or oxygen metabolism was not significantly altered by FM.[13,16] It has also been reported that subjects with FM have prolonged oxygen level (oxy- and deoxyhemoglobin concentrations) recovery times following muscle ischemia[18] or aerobic exercise.[19] The previous studies provide incomplete information, and simultaneous measurements of tissue blood flow, blood oxygenation and oxygen metabolism are required for a more comprehensive evaluation of dynamic skeletal muscle and circulatory functions in FM.

Methods previously used to measure muscle blood flow, oxygenation and oxygen consumption in FM population all have limitations. Laser Doppler cannot detect blood flow in deep muscle tissue, and is limited to superficial layers (such as skin).[8] The Xe133 technique[12,16,20] or contrast media-enhanced color ultrasound Doppler[17] can measure microvasculature blood flow in deep muscle tissue; however the invasive and complex procedure of injecting radioactive isotopes or contrast agents limits their widespread use in the clinic. Partial pressure of oxygen (PO2) electrodes have been used to invasively assess muscle oxygenation in a tiny spot,[21] which may not be representative of the whole skeletal muscle. Phosphorus magnetic resonance spectroscopy (P-31 MRS) has been used to assess muscle oxygen consumption,[14] but does not provide high temporal resolution and requires large and expensive instrumentation.[22]

Near-infrared diffuse optical spectroscopy (NIRS) offers a noninvasive, rapid, portable, and low-cost alternative for monitoring tissue blood oxygenation and oxygen consumption in microvasculature, although it does not directly measure tissue blood flow. Near-infrared light probes tissue millimeters to centimeters below the skin surface, allowing for measurement of oxy- and deoxyhemoglobin concentrations ([HbO2] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO2).[23] NIRS has been broadly used for noninvasive assessment of tissue oxygenation in clinic. According to a review paper written by Ferrari et al.,[24] approximately160 articles on the use of NIRS to study muscle physiology (primarily in upper and lower limb muscles) were published from 2007 up to the end of 2010.[24] NIRS has also been used in studies of FM[18,19] and CFS[5,25] to evaluate tissue hemodynamic responses following muscle ischemia and aerobic exercise. Near-infrared diffuse correlation spectroscopy (DCS) is an emerging technique capable of directly and noninvasively measuring microvascular blood flow in various tissues, including human skeletal muscles.[23,26–28] DCS combines several attractive features for blood flow measurement including noninvasiveness, high temporal resolution (up to several milliseconds),[29] portability, and relatively large penetration depth (up to several centimeters).[30,31] DCS for blood flow measurement in various organs and tissues have been validated to other standards, including laser Doppler,[32,33] Xenon-CT,[34] fluorescent microsphere flow measurement,[35] and perfusion magnetic resonance imaging (perfusion MRI).[36] Recently, our group has developed a hybrid diffuse optical instrument which combines a commercial NIRS tissue oximeter (Imagent, ISS Inc., IL, USA) and a custom-designed DCS tissue flowmeter for measurements of both tissue blood flow and blood oxygenation.[23] Simultaneous measurements of blood flow and oxygenation enable estimation of the oxygen metabolic rate in tissue,[27] thus providing comprehensive information about dynamic tissue oxygen kinetics.

The present study aims to use the hybrid NIRS/DCS instrument to evaluate skeletal muscle tissue hemodynamics (blood flow and oxygenation) and oxygen metabolism in postmenopausal women with and without FM. Because the abnormality of oxygen kinetics in FM may not be apparent at rest, leg skeletal muscle hemodynamics and metabolism were manipulated by isometric fatiguing exercise. In addition, a protocol of temporary cuff occlusion was used to create muscle ischemia in the forearm and to monitor muscle blood flow and oxygen recovery dynamics during reactive hyperemia. To the best of our knowledge, this study quantified for the first time, skeletal muscle hemodynamics and metabolism simultaneously in subjects with FM and well-matched healthy controls during exercise and during a muscle ischemic challenge. We hypothesize that FM affects muscle hemodynamic/metabolic responses to fatiguing exercise and ischemic challenge, which can be detected by our hybrid NIRS/DCS instrument. This study provided comprehensive and comparative evaluation of muscle oxygen kinetics to improve the understanding of the physiological mechanisms of FM.

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