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


Arthritis Res Ther. 2012;14(6) 

In This Article


Although previous studies have individually measured skeletal muscle blood flow,[8,12,16,17,20] oxygenation[18,19,21] or oxygen consumption[14] in the FM population, none have investigated all these variables simultaneously in a single study. While NIRS and DCS have provided a great deal of hemodynamic data individually, both must be used in order to evaluate rOEF and rVO2. The present study reports the first results using the novel hybrid diffuse optical instrument for simultaneous monitoring of muscle blood flow, oxygenation during fatiguing leg exercise and during arm cuff occlusion, from which muscle oxygen extraction and consumption rate were derived. Both protocols, cuff occlusion and fatiguing exercise, created an imbalance between tissue oxygen supply (blood flow) and oxygen consumption for challenging muscle function. Cuff occlusion is a static protocol which creates tissue ischemia during occlusion and reactive hyperemia after release of occlusion. Fatiguing exercise is a dynamic exercise protocol which tests muscle regulatory and metabolic responses to stimulus (that is, exercise). Both protocols have been widely used to assess a variety of diseases affecting skeletal muscle, including peripheral arterial disease,[27] CFS,[5] and FM.[18,19] We adopted both protocols in the present study to extensively evaluate muscle oxygen and flow kinetics in both healthy and FM populations. We demonstrated in this study that the hybrid instrument has high sensitivity in detecting hemodynamic and metabolic responses to muscle ischemia/reperfusion and fatiguing exercise.

Subjects with FM had similar hemodynamic and metabolic response/recovery patterns to healthy controls during exercise and during arterial occlusion, and most measured variables did not show significant differences between the two groups. However, we observed that rOEF during exercise in subjects with FM were significantly lower than those in healthy controls (see Figure 3), and the half-times of oxygenation recovery (Δ[HbO2] and Δ[Hb]) were significantly longer (see Figure 5 and Figure 7).

Both lower rOEF and longer oxygenation recovery time indicate an impairment of oxygen utilization in subjects with FM. Although not tested in this study, these findings could reflect altered mitochondrial function. The pain and fatigue in subjects with FM have been found by others to be associated with mitochondrial dysfunction,[6] as evidenced by decreased coenzyme Q10 (CoQ10), increased oxidative stress, as well as increased reactive oxygen species (ROS) production.[6] Mitochondrial dysfunction could also cause abnormal synthesis of adenosine-triphosphate (ATP), resulting in insufficient energy supply and muscle fatigue.[6] Accordingly, FM may impact mitochondrial oxidation to meet the increased metabolic demand during exercise, which would lead to a lower rOEF as observed in the present study.

On the other hand, following fatiguing exercise and cuff occlusion, extra oxygen is needed to compensate the oxygen loss in hemoglobin during exercise, and to oxidize lactate generated from anaerobic respiration.[49] This process is termed 'repaying the oxygen debt'.[50] Here, oxygen debt represents the oxygen deficit due to the imbalance between oxygen consumed by the tissue and that supplied via blood during exercise or muscle ischemia. Oxygenation recovery is dependent on the restoration of tissue microcirculation (that is, blood flow recovery) as well as the amount of oxygen debt to be repaid. We found in both exercise and occlusion protocols that the half-times of Δ[HbO2] and Δ[Hb] in subjects with FM were significantly longer than those in healthy controls (see Figure 5 and Figure 7), which is consistent with previous study findings using a cuff occlusion protocol or treadmill exercise.[18,19] The prolonged oxygenation recovery has been attributed to the imbalance between the oxygen supply and demand,[18] although blood flow was not measured in those studies. In the present study, the FM group did not show a significant deficit in rBF recovery, so the prolonged oxygen recovery was independent of reactive hyperemia, but rather due to a higher oxygen debt. A higher oxygen debt in FM subjects was also observed in other studies,[4,11,51,52] where subjects with FM were found to have a higher concentration of muscle lactate during anaerobic respiration. Fatiguing exercise[53] and muscle ischemic challenge[54] as used in the present study could induce extra muscle blood lactate in FM subjects. Lactate accumulation was recently proposed to be associated with muscle pain in FM subjects,[55] although controversy remains.[56] Our findings suggest a future direction to explore the FM-induced alterations in mitochondrial function and lactate accumulation. An investigation of the relationships among oxygen kinetics, mitochondrial function and lactate dynamics are needed to further explore the origin of pain and fatigue in FM.

The present study is limited to the relative measurements of muscle blood flow, oxygen extraction fraction and oxygen consumption rate. However, some clinical outcomes, such as muscle capillary density, are found to be closely associated with the absolute values of muscle blood flow and oxygen consumption rate.[57,58] In addition, the blood flow index with a unit of cm2/s measured by DCS, needs to be calibrated to a classical blood flow unit of ml/min/100 ml for biological tissues. Another limitation is that we used the 6-second average data immediately after fatiguing exercise to represent the exercise-induced responses, as the optical data during exercise were contaminated by the muscle motion artifacts.[26] Although this method has been widely used in other exercise studies,[46,47] it may generate measurement errors since muscle hemodynamics/metabolism change rapidly immediately after exercise. To overcome those limitations, we are currently designing calibration methods to obtain absolute tissue blood flow and VO2, as well as gating algorithms to reduce motion artifacts during exercise.[59]