Rationale and Objectives
The aim of the work described here was to determine the feasibility of monitoring Na + concentration and distribution in muscle/skin during aerobic/anaerobic exercise with 23 Na magnetic resonance imaging (MRI).
Materials and Methods
The Na + concentration and water content of muscle/skin of the left lower leg of six healthy subjects (mean age, 26 years; range, 22–30 years; three men and three women) were assessed before and after aerobic/anaerobic cycle ergometry and during recovery with 3-T 23 Na/ 1 H MRI. 23 Na MRI was performed with a custom-made knee coil. A gradient echo sequence with an acquisition time of 3.25 minutes, echo time of 2.07 ms, repetition time of 100 ms, and spatial resolution of 3 × 3 × 30 mm 3 was applied. Phantoms with increasing sodium concentration served for quantification via linear extrapolation. Blood values were determined by blood gas analysis.
Results
The concentration of Na + significantly increased during anaerobic exercise in all muscle compartments except the medial gastrocnemius muscle, whereas no significant change was observed in most muscle compartments during aerobic exercise (only the soleus muscle exhibited a significant increase in Na + concentration during aerobic exercise: 1.6 ± 1.5 mmol/kg, 4.5%, P = .046). During anaerobic exercise, the mean Na + concentration of the triceps surae and the whole leg increased by 9.0% (3.1 ± 2.1 mmol/kg, P = .016) and 6.5% (2.2 ± 1.3 mmol/kg, P < .01). MRI revealed a water-independent increase in Na + concentration in most muscle compartments during anaerobic exercise. Na + concentration significantly decreased during recovery after anaerobic and aerobic exercise in all muscle compartments except the soleus. The Na + concentration of the skin did not significantly change during anaerobic/aerobic exercise.
Conclusions
Sodium 23 MRI allows reliable and noninvasive visualization and quantification of Na + concentration and distribution in muscle and skin during exercise. 23 Na MRI can be used to gain new insights into Na + homeostasis, presumably leading to better comprehension of pathophysiology.
The physiology of skeletal muscles can be examined with magnetic resonance imaging (MRI). After exercise, the skeletal muscle T2 relaxation value increases, resulting in a gain in signal intensity on T2-weighted 1 H MRI . The predominant cause is the intracellular accumulation of metabolites (eg, lactate) and the resulting osmotic shift of water from the extracellular to the intracellular space . Recently published studies indicate that 23 Na MRI has the potential to provide insight into muscle physiology . We have described the relevance of this regulatory system to salt-sensitive hypertension . Furthermore, in long-term balance studies by our group, we documented infradian rhythms in Na + balance and excretion that are highly consistent with an additional Na + storage compartment . We used carcass ashing and atomic absorption spectrometry, methods that clearly that have no human application . To study patients and normal subjects, we developed 23 Na MRI. We constructed a coil for 23 Na MRI with the upper calf as a target that allows skin, skeletal muscle, and bone to be investigated. In earlier studies, we validated the utility of this method in experimental animals and human subjects, including patients on hemodialysis .
It is well known that there are large concentration differences in sodium (Na + ) and potassium (K + ) between the intracellular and extracellular spaces, resulting in potential differences over membranes. In skeletal muscle, a low concentration of Na + (10–30 mmol/L) and a high concentration of K + (140 mmol/L) predominate intracellularly. In contrast, the extracellular concentrations are 145 mmol/L for Na + and 4 mmol/L for K + . Responsible for this gradient over the membrane is Na + /K + -ATPase (adenosine triphosphatase), which pumps 3 Na + ions from the intracellular to the extracellular space and 2 K + ions in the reverse direction. Muscle contraction–initiating action potentials cause a sudden influx of Na + ions and efflux of K + ions. During exercise, these ion shifts degrade the transmembrane gradients, leading to increasing loss of membrane excitability and muscle contractility, which are believed to be the main causes of muscle fatigue .
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Materials and methods
Participant Recruitment and Experimental Setup
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Table 1
Characteristics of the Participants
Gender 3 Female, 3 male Age, y 25.8 ± 2.9 (range, 23–30) Anaerobic Exercise Aerobic Exercise Body mass index 23.3 ± 2.9 (range, 18.1–25.8) 23.4 ± 2.9 (range, 18.2–25.7) Heart rate before exercise, 1/min 90.8 ± 10.9 80.2 ± 15.4 Maximum heart rate during exercise, 1/min 191.3 ± 6.2 123.3 ± 13.1 Blood pressure before exercise, mm Hg 123/75 ± 9/3 111/70 ± 11/7 Maximum blood pressure during exercise, mm Hg 193/94 ± 30/35 133/64 ± 8/6 Maximum ergometer workload, W 200 ± 54 71 ± 29
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Imaging Technique
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Table 2
Scanning Protocol
Parameter Localizer T1-Weighted Fast-Low-Angle-Shot Sequence Fat-Suppressed Inversion Recovery Sequence Gradient Echo 23 Na Sequence (Acquired 4 Times Successively) Total acquisition time (min) 0.15 2.08 6.22 3.25 Echo time (ms) 4 2.46 12 2.07 Repetition time (ms) 8.6 250 3000 100 Inversion time (ms) — — 210 — Flip angle (°) 20 60 90/180 90 Averages 2 2 1 32 Bandwidth (Hz/pixel) 320 310 130 430 Field of view (mm) 192 192 192 192 Matrix (pixel) 256 256 128 64 Resolution (mm) 0.75 × 0.75 × 10 0.75 × 0.75 × 5 1.5 × 1.5 × 5 3 × 3 × 30
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Image Analysis
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Statistical Analysis
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Results
Image Quality Evaluation
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Tissue Na + Concentration During Anaerobic and Aerobic Exercise
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Table 3
Tissue Na + Concentration and Water Content (Determined by 23 Na/ 1 H MRI) and Clinical Data/Blood Levels Before Anaerobic (B) and Aerobic Exercise (B′) Exercise, Immediately After Anaerobic (A) and Aerobic (A′) Exercise, and After 50 Min of Recovery (R/R′)
Anaerobic Exercise Aerobic Exercise B A R B′ A′ R′ Na + (mmol/kg) Triceps surae muscle Mean ± SD 34.5 ± 3.7 37.6 ± 3.8 34.3 ± 1.8 34.4 ± 2.7 35.9 ± 2.0 34.0 ± 2.1 Δ (%) 9.0 −8.8 4.3 −5.4P value .016 .014 .117 .015 Peroneal and superficial extensor muscles Mean ± SD 31.9 ± 2.5 35.3 ± 3.7 31.4 ± 1.8 31.9 ± 1.6 33.6 ± 2.1 31.8 ± 1.7 Δ (%) 10.9 −11.3 5.6 −5.4P value .005 .015 .055 .007 Medial gastrocnemius muscle Mean ± SD 34.1 ± 6.4 36.8 ± 5.3 33.1 ± 2.4 33.5 ± 2.8 34.2 ± 2.2 31.9 ± 2.2 Δ (%) 7.8 −9.8 1.9 −6.8P value .085 .033 .483 .012 Lateral gastrocnemius muscle Mean ± SD 34.4 ± 4.9 38.9 ± 2.9 33.9 ± 2.3 34.9 ± 5.5 36.8 ± 2.9 33.8 ± 2.8 Δ (%) 13.2 −12.7 5.3 −8.1P value .032 .000143 .309 .006 Soleus muscle Mean ± SD 34.9 ± 1.9 37.9 ± 3.5 35.4 ± 1.6 35.3 ± 1.6 36.9 ± 1.8 35.5 ± 1.9 Δ (%) 8.6 −6.6 4.5 −3.9P value .013 .060 .046 .095 Skin Mean ± SD 49.7 ± 4.2 50.7 ± 4.2 49.1 ± 3.8 51.9 ± 6.0 50.3 ± 4.3 49.7 ± 4.9 Δ (%) 2.0 −3.1 −3.1 −1.3P value .215 .102 .104 .192 Bone marrow Mean ± SD 16.5 ± 4.4 18.2 ± 5.1 19.1 ± 5.4 19.6 ± 5.3 17.6 ± 5.3 18.1 ± 6.6 Δ (%) 10.5 4.9 −10.0 2.7P value .453 .735 .324 .833 Whole leg Mean ± SD 34.0 ± 2.2 36.2 ± 1.8 33.5 ± 1.6 34.5 ± 2.7 35.4 ± 1.7 33.9 ± 2.1 Δ (%) 6.5 −7.2 2.7 −4.1P value .008 .007 .155 .007 H 2 O (kg/L) Triceps surae muscle Mean ± SD 0.49 ± 0.03 0.50 ± 0.02 0.50 ± 0.02 0.49 ± 0.01 0.50 ± 0.02 0.49 ± 0.01 Δ (%) 1.6 −1.0 1.9 −1.0P value .212 .192 .034 .194 Peroneal and superficial extensor muscles Mean ± SD 0.50 ± 0.03 0.51 ± 0.03 0.50 ± 0.03 0.50 ± 0.02 0.51 ± 0.02 0.51 ± 0.02 Δ (%) 2.7 −2.5 3.5 −1.7P value .020 .102 .024 .107 Medial gastrocnemius muscle Mean ± SD 0.46 ± 0.03 0.46 ± 0.02 0.45 ± 0.02 0.45 ± 0.02 0.45 ± 0.01 0.44 ± 0.01 Δ (%) 0.3 −2.2 0.9 −2.1P value .851 .083 .217 .032 Lateral gastrocnemius muscle Mean ± SD 0.54 ± 0.04 0.56 ± 0.04 0.54 ± 0.03 0.54 ± 0.04 0.54 ± 0.04 0.53 ± 0.03 Δ (%) 2.4 −2.0 −0.3 −1.0P value .379 .132 .843 .438 Soleus muscle Mean ± SD 0.51 ± 0.02 0.52 ± 0.02 0.52 ± 0.02 0.51 ± 0.01 0.52 ± 0.04 0.52 ± 0.01 Δ (%) 1.6 0.3 3.0 −0.2P value .137 .635 .018 .787 Skin Mean ± SD 0.08 ± 0.03 0.07 ± 0.03 0.07 ± 0.04 0.09 ± 0.04 0.07 ± 0.03 0.08 ± 0.03 Δ (%) −6.5 3.8 −14.7 3.8P value .157 .388 .063 .132 Bone marrow Mean ± SD 0.05 ± 0.02 0.07 ± 0.02 0.06 ± 0.02 0.07 ± 0.01 0.06 ± 0.02 0.06 ± 0.02 Δ (%) 27.4 −14.7 −6.0 −13.4P value .041 .073 .625 .061 Whole leg Mean ± SD 0.34 ± 0.04 0.35 ± 0.04 0.34 ± 0.04 0.34 ± 0.04 0.35 ± 0.04 0.34 ± 0.04 Δ (%) 2.3 −1.7 2.1 −1.5P value .082 .073 .042 .125 Clinical Body weight (kg) Mean ± SD 70.8 ± 8.4 70.6 ± 8.3 70.4 ± 8.3 71.1 ± 8.3 71.0 ± 8.3 71.0 ± 8.3 Δ (%) −0.4 −0.2 −0.1 −0.1P value .004 .025 .041 .025 Blood Na + (mmol/L) Mean ± SD 139.8 ± 1.9 144.5 ± 4.0 140.0 ± 2.3 140.8 ± 1.3 141.8 ± 1.7 140.0 ± 1.9 Δ (%) 3.3 −3.1 0.7 −1.3P value .005 .003 .144 .020 Blood K + (mmol/L) Mean ± SD 3.7 ± 0.1 4.8 ± 0.5 4.2 ± 0.4 3.9 ± 0.6 4.0 ± 0.5 5.0 ± 1.6 Δ (%) 29.5 −13.8 3.9 24.6P value .004 .006 .560 .180 Blood lactate (mmol/L) Mean ± SD 1.2 ± 0.3 11.2 ± 2.8 1.8 ± 1.1 1.0 ± 0.2 1.1 ± 0.6 0.8 ± 0.2 Δ (%) 877.4 −83.7 7.1 −28.3P value .0002 .0001 .816 .276 Blood pH Mean ± SD 7.4 ± 0.03 7.2 ± 0.1 7.4 ± 0.02 7.4 ± 0.02 7.4 ± 0.03 7.4 ± 0.03 Δ (%) −2.0 2.1 0.4 −0.1P value .003 .002 .111 .295 Blood bicarbonate (mmol/L) Mean ± SD 25.7 ± 1.6 16.6 ± 1.1 24.7 ± 1.8 25.5 ± 2.2 24.6 ± 2.2 25.6 ± 2.2 Δ (%) −35.6 49.0 −3.6 4.2P value .00009 .0003 .332 .14 Blood anion gap (mmol/L) Mean ± SD 6.2 ± 2.9 16.6 ± 5.0 6.5 ± 2.1 5.7 ± 1.9 6.5 ± 1.9 4.1 ± 3.2 Δ (%) 169.0 −60.9 15.0 −37.8P value .00037 .001 .34 .042
SD, standard deviation.
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Water Content in the Course of Anaerobic and Aerobic Exercise
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Clinical Data and Blood Levels
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Discussion
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Conclusions and perspectives
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Acknowledgments
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