Original contributionSex differences in sodium deposition in human muscle and skin
Introduction
Sodium is the most abundant cation in the human body, and is vital for cellular function and integrity [1], [2]. Normally, the intracellular space accounts for 80% of tissue volume with a sodium concentration of 10–15 mM, against an extracellular volume fraction of 20% with a sodium concentration of 140–150 mM. This relatively stable concentration difference is primarily maintained by the sodium-potassium Na+/K+-ATPase pump, which pumps sodium out of cells while pumping potassium into cells. Leaky cell membranes or impaired Na+/K+ exchange kinetics potentially change the cytosolic total tissue sodium, making sodium a biomarker of a wide range of disease states [3], [4], [5], [6], such as stroke, cancer, osteoarthritis, neurological disorders, edema, and acute myocardial infarction. Typically, an increase of total tissue sodium concentration (TSC) indicates a loss of tissue viability and is associated with an increase of intracellular sodium due to the loss of integrity of the cell, and also with an increase of extracellular volume when cells are dying [1], [7], [8], [9], [10], [11], [12].
The first investigation of sodium NMR in biological tissues was piloted in the early 1970s [13], [14], while the feasibility of sodium MRI in human subjects and its potential use for detecting pathological changes were demonstrated in the middle to late 1980s [3], [8], [9], [15]. Interest in the use of sodium MRI has increased over time due to the availability of higher magnetic fields, improved hardware and pulse sequences [4], [16], and the availability of ultra-high field MRI scanners (7 T and 9.4 T) [17], [18], [19]. Further improvements in electronics, RF coils, and acquisition techniques [20], [21], [22] have made sodium MRI feasible at reasonable resolution in practical scan times. To date, sodium MRI has been applied to image several human organs in vivo including brain, heart, cartilage, kidney, breast, spine, as well as muscle and skin [6], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34].
In muscle, sodium changes can be linked to several disease states, including diabetes mellitus, starvation, hypothyroidism, hypertension, and cardiovascular risk. Skin sodium has been studied relatively rarely compared to muscle. Recent studies have shown that sodium may be sequestered in both skin and muscle so that tissue sodium levels are not reliably measured by sampling blood or interstitial fluid, which has important implications for the management of hypertension and kidney disease [33]. Therefore, measurements of sodium concentrations in skin or muscle may be a useful biomarker of risk of disease progressions, but the interpretation of such measurements will rely on understanding the factors that affect sodium levels.
A previous study observed that sodium in muscle and skin appeared to change differently with age for men and women. Specifically, it noted an increase of sodium storage in skin for both men and women, and an increase of sodium storage in muscle for men, but not women [33]. In our recent preliminary studies [35], [36], we observed that the sodium deposition between muscle and skin was sex-relevant. For males, skin sodium content appeared higher than muscle sodium, which was opposite to females who tended to have higher muscle sodium than skin. Prompted by these observations, we investigate whether this sex specific pattern of sodium deposition in muscle and skin is statistically significant.
Section snippets
Materials and methods
This study was approved by the Institutional Review Board (IRB) of the Vanderbilt University. A total of thirty eight (38) subjects: 20 males, aged 25–79 with a median age of 51; 18 females, aged 38–66 years, with a median age of 53 were recruited. The demographic characteristics of the subjects are included in Table 1. Written informed consent from each subject was obtained prior to MR imaging.
Results
Table 1 summarizes the demographic information and TSC in muscle and skin for males and females, along with the calculation of ΔTSC (= TSCmuscle − TSCskin). Notably, a majority of the males have higher TSC in skin than in muscle, while female muscle TSC is greater than skin TSC. The Wilcoxon rank sum test confirms the sex difference in sodium deposition between muscle and skin is significantly different (P = 3.10 × 10− 5). The multiple linear regression also shows a statistically significant effect of
Discussion
Our results show there are different patterns of sodium accumulation in muscle and skin for men and women, a difference that appears to increase with age. The MRI method used is able to unambiguously differentiate sodium in muscles and skin of the leg and quantify spatial differences in concentration with good precision and spatial resolution. These findings are relevant to the interpretation of sodium measurements that may be used to follow changes over time in, for example, patients with
Acknowledgements
The work was supported by NIH T32 EB001628, and the Vanderbilt University Institute of Imaging Science (VUIIS) internal funds.
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