Changes In Sodium Concentration Research Articles

A Multienzyme Logic H+ and Na+ Biotransducer.

Sodium ions and protons regulate various fundamental processes at the cell and tissue levels across all biological kingdoms. It is therefore pivotal for bioelectronic devices, such as biosensors and biotransducers, to control the transport of these ions through biological membranes. Our study explores the regulation of proton and sodium concentrations by integrating an Na+-type ATP synthase, a glucose dehydrogenase (GDH), and a urease into a multienzyme logic system. This system is designed to operate using various chemical control input signals, while the output current corresponds to the local change in proton or sodium concentrations. Therein, a H+ and Na+ biotransducer was integrated to fulfill the roles of signal transducers for the monitoring and simultaneous control of Na+ and H+ levels, respectively. To increase the proton concentration at the output, we utilized GDH driven by the inputs of glucose and nicotinamide adenine dinucleotide (NAD+), while recorded the signal change from the biotransducer, together acting as an AND enzyme logic gate. On the contrary, we introduced urease enzyme which hydrolyzed urea to control the decrease in proton concentration, serving as a NOT gate and reset. By integrating these two enzyme logic gates we formed a simple multienzyme logic system for the control of proton concentrations. Furthermore, we also demonstrate a more complex, Na+-type ATP synthase-urease multienzyme logic system, controlled by the two different inputs of ADP and urea. By monitoring the voltage of the peak current as the output signal, this logic system acts as an AND enzyme logic gate. This study explores how multienzyme logic systems can modulate biologically important ion concentrations, opening the door toward advanced biological on-demand control of a variety of bioelectronic enzyme-based devices, such as biosensors and biotransducers.

A Multienzyme Logic H+ and Na+ Biotransducer.

Sodium ions and protons regulate various fundamental processes at the cell and tissue levels across all biological kingdoms. It is therefore pivotal for bioelectronic devices, such as biosensors and biotransducers, to control the transport of these ions through biological membranes. Our study explores the regulation of proton and sodium concentrations by integrating an Na+-type ATP synthase, a glucose dehydrogenase (GDH), and a urease into a multienzyme logic system. This system is designed to operate using various chemical control input signals, while the output current corresponds to the local change in proton or sodium concentrations. Therein, a H+ and Na+ biotransducer was integrated to fulfill the roles of signal transducers for the monitoring and simultaneous control of Na+ and H+ levels, respectively. To increase the proton concentration at the output, we utilized GDH driven by the inputs of glucose and nicotinamide adenine dinucleotide (NAD+), while recorded the signal change from the biotransducer, together acting as an AND enzyme logic gate. On the contrary, we introduced urease enzyme which hydrolyzed urea to control the decrease in proton concentration, serving as a NOT gate and reset. By integrating these two enzyme logic gates we formed a simple multienzyme logic system for the control of proton concentrations. Furthermore, we also demonstrate a more complex, Na+-type ATP synthase-urease multienzyme logic system, controlled by the two different inputs of ADP and urea. By monitoring the voltage of the peak current as the output signal, this logic system acts as an AND enzyme logic gate. This study explores how multienzyme logic systems can modulate biologically important ion concentrations, opening the door toward advanced biological on-demand control of a variety of bioelectronic enzyme-based devices, such as biosensors and biotransducers.

Resting membrane potential and intracellular [Na+] at rest, during fatigue and during recovery in rat soleus muscle fibres in situ.

Large trans-sarcolemmal ionic shifts occur with fatiguing exercise or stimulation of isolated muscles. However, it is unknown how resting membrane potential (EM) and intracellular sodium concentration ([Na+]i) change with repeated contractions in living mammals. We investigated (i) whether [Na+]i (peak, kinetics) can reveal changes of Na+-K+ pump activity during brief or fatiguing stimulation and (ii) how resting EM and [Na+]i change during fatigue and recovery of rat soleus muscle in situ. Muscles of anaesthetised rats were stimulated with brief (10s) or repeated tetani (60Hz for 200ms, every 2s, for 30s or 300s) with isometric force measured. Double-barrelled ion-sensitive microelectrodes were used to quantify resting EM and [Na+]i. Post-stimulation data were fitted using polynomials and back-extrapolated to time zero recovery. Mean pre-stimulation resting EM (layer 2-7 fibres) was -71mV (surface fibres were more depolarised), and [Na+]i was 14mM. With deeper fibres, 10s stimulation (2-150Hz) increased [Na+]i to 38-46mM whilst simultaneously causing hyperpolarisations (7.3mV for 2-90Hz). Fatiguing stimulation for 30s or 300s led to end-stimulation resting EM of -61 to -53mV, which recovered rapidly (T1/2, 8-22s). Mean end-stimulation [Na+]i increased to 86-101mM with both fatigue protocols and the [Na+]i recovery time-course (T1/2, 21-35s) showed no difference between protocols. These combined findings suggest that brief stimulation hyperpolarises the resting EM, likely via maximum Na+-induced stimulation of the Na+-K+ pump. Repeated tetani caused massive depolarisation and elevations of [Na+]i that together lower force, although they likely interact with other factors to cause fatigue. [Na+]i recovery kinetics provided no evidence of impaired Na+-K+ pump activity with fatigue. KEY POINTS: It is uncertain how resting membrane potential, intracellular sodium concentration ([Na+]i), and sodium-potassium (Na+-K+) pump activity change during repeated muscle contractions in living mammals. For rat soleus muscle fibres in situ, brief tetanic stimulation for 10s led to raised [Na+]i, anticipated to evoke maximal Na+-induced stimulation of the Na+-K+ pump causing an immediate hyperpolarisation of the sarcolemma. More prolonged stimulation with repeated tetanic contractions causes massive elevations of [Na+]i, which together with large depolarisations (via K+ disturbances) likely reduce force production. These effects occurred without impairment of Na+-K+ pump function. Together these findings suggest that rapid activation of the Na+-K+ pump occurs with brief stimulation to maintain excitability, whereas more prolonged stimulation causes rundown of the trans-sarcolemmal K+ gradient (hence depolarisation) and Na+ gradient, which in combination can impair contraction to contribute to fatigue in living mammals.

#2707 Prediction of plasma sodium changes in hypernatremic patients: the role of tissue sodium content

Abstract Background and Aims Hypo- and hypernatremia are frequently encountered electrolyte disturbances in clinical practice. Rapid correction of these dysnatremias can result in severe neurological complications. Therefore, various formulas have been developed to predict changes in plasma sodium concentration ([Na+]) after treatment. However, these kidney-centered formulas have been shown to be inaccurate. A potential explanation for the discrepancy between predicted and measured plasma [Na+] is the accumulation of sodium in the skin, which is not explicitly taken into account in these formulas. The purpose of this post-hoc analysis is to evaluate the association between factors related to tissue sodium accumulation and the discrepancy between measured and predicted plasma [Na+]. Method We used data from a hypernatremic intensive care unit (ICU) cohort with 66 patients and 1,034 ICU days with complete data on sodium, potassium and water balance. We excluded ICU days with incomplete balances, dialysis and severe diarrhea. The predicted plasma [Na+] was calculated using the Barsoum-Levine (BL) and the Nguyen-Kurtz (NK) formula. Then, we calculated the discrepancy between predicted and measured plasma [Na+] (∆[Na+]). We fitted a linear mixed-effect model to investigate the association between factors related to tissue sodium content and ∆[Na+]. Age, sex, blood pressure, eGFR, CRP, plasma albumin, total body water (TBW), baseline plasma [Na+] and changes in plasma [Na+] were incorporated as fixed effects in the model, while the subjects were introduced as a random effect. TBW was estimated as 60% of body weight for males and 50% of body weight for females, corrected for fluid balances on subsequent ICU days. Results A total of 613 ICU days of 66 patients were included in our analysis. The mean age was 58 ± 15 years and 38% was female. The mean plasma [Na+] at inclusion day was 145 ± 9 mmol/L and mean eGFR CKD-EPI was 52 ± 28 ml/min/1.73 m2. On average, the deviation between predicted and measured plasma [Na+] was 3.8 ± 3.3 mmol/L for the BL formula and 3.9 ± 3.4 mmol/L for the NK formula. For both formulas, TBW (p = 0.01), baseline plasma [Na+] (p < 0.001) and plasma [Na+] change (p < 0.001) were significantly associated with the discrepancy between predicted and measured plasma [Na+] (Table 1). Plasma albumin (p = 0.02) was also significantly associated with this discrepancy when the NK formula was used. Conclusion In a hypernatremic ICU cohort, baseline plasma [Na+], estimated TBW and plasma [Na+] changes are associated with the inaccurateness of plasma [Na+] prediction. As baseline plasma [Na+] and estimated TBW are available when initiating treatment, incorporation of these variables in the currently available formulas may improve the prediction of plasma [Na+].

Comparative Safety and Effectiveness of Urea and Tolvaptan for the Management of Hyponatremia.

Background: The optimal management of euvolemic and hypervolemic hyponatremia remains controversial. The effectiveness of the vasopressin receptor antagonist tolvaptan on serum sodium normalization has been well described in the literature, although the associated risk of serum sodium overcorrection limits its use. Urea has been proposed as an alternative treatment option due to its milder serum sodium raising effects and adverse event profile. Objective: This study aimed to compare urea and tolvaptan for their serum sodium raising effects and potential for overcorrection. Methods: In a multicenter retrospective review, 46 hospitalized patients who received either urea or tolvaptan for the management of hyponatremia were evaluated for the rate of serum sodium normalization and overcorrection. Results: Mean serum sodium concentrations at baseline were 125.91mEq/L and 123.83mEq/L for patients treated with urea and tolvaptan, respectively. After 12 hours, tolvaptan was associated with a significantly higher rate of serum sodium increase compared with urea (5.05mEq/L vs 1.10mEq/L; P = .001). However, no statistically significant differences were observed in the mean change in serum sodium concentrations at 24hours, 48hours, or with the proportion of patients who reached a serum sodium concentration of 135mEq/L. Overcorrection rates were significantly higher with tolvaptan compared with urea at 43% and 9%, respectively. Conclusion: The results of this study suggest that urea has a comparable effectiveness profile to tolvaptan for the management of hyponatremia with a significantly reduced risk of overcorrection.

Relationship between the behavior change model and salt intake in hypertensive patients: a single non-specialized hypertension clinic prospective observational study.

We investigated whether changes in salt reduction readiness are associated with changes in estimated daily salt intake and blood pressure (BP). We divided 86 hypertensive patients into groups with high and low readiness for salt-reducing behavior [an up (UP) and a down (DN) groups, respectively] based on the transtheoretical model (TTM) over a 12-month observation period. We then investigated the relationships between changes in the TTM stage and changes in daily salt intake and BP over 12 months. The patients in the UP group had significantly increased urine potassium concentrations (from 51.2 ± 23.3 mEq/L at baseline to 56.9 ± 25.5 mEq/L at 12 months; P = 0.048) and significantly decreased estimated 24-h urinary salt excretion (from 9.7 ± 2.9 g/day at baseline to 8.4 ± 2.8 g/day at 12 months; P = 0.045). In addition, they also had significantly lower changes in urine sodium concentration (-13.1 ± 46.1 vs. -6.6 ± 59.7 mEq/L; P = 0.048), significantly increased changes in urine potassium concentration (5.7 ± 20.1 vs. -4.8 ± 28.6 mEq/L; P = 0.030), and significantly decreased changes in estimated 24-h urinary salt excretion (-1.3 ± 2.6 vs. -0.1 ± 2.6 g/day; P = 0.045) compared with patients in the DN group. However, their home BP did not improve over 12 months. The hypertensive patients who increased their readiness or maintained a high readiness for salt reduction over 12 months showed a significant increase in daily potassium intake and significant decrease in daily salt intake.

Longitudinal changes in sodium concentration and in clinical outcome in mild traumatic brain injury.

Ionic imbalances and sodium channel dysfunction, well-known sequelae of traumatic brain injury (TBI), promote functional impairment in affected subjects. Therefore, non-invasive measurement of sodium concentrations using 23Na MRI has the potential to detect clinically relevant injury and predict persistent symptoms. Recently, we reported diffusely lower apparent total sodium concentrations (aTSC) in mild TBI patients compared to controls, as well as correlations between lower aTSC and worse clinical outcomes. The main goal of this study was to determine whether these aTSC findings, and their changes over time, predict outcomes at 3- and 12-month from injury. Twenty-seven patients previously studied with 23Na MRI and outcome measures at 22 ± 10 days (average ± standard deviation) after injury (visit-1, v1) were contacted at 3- (visit-2, v2) and 12-month after injury (visit-3, v3) to complete the Rivermead post-concussion symptoms questionnaire (RPQ), the extended Glasgow outcome scale (GOSE), and the brief test of adult cognition by telephone (BTACT). Follow-up 1H and 23Na MRI were additionally scheduled at v2. Linear regression was used to calculate aTSC in global grey and white matters. Six hypotheses were tested in relation to the serial changes in outcome measures and in aTSC, and in relation to the cross-sectional and serial relationships between aTSC and outcome. Twenty patients contributed data at v2 and fifteen at v3. Total RPQ and composite BTACT z-scores differed significantly for v2 and v3 in comparison to v1 (each P < 0.01), reflecting longitudinally reduced symptomatology and improved performance on cognitive testing. No associations between aTSC and outcome were observed at v2. Previously lower grey and white matter aTSC normalized at v2 in comparison to controls, in line with a statistically detectable longitudinal increase in grey matter aTSC between v1 and v2 (P = 0.0004). aTSC values at v1 predicted a subset of future BTACT subtest scores, but not future RPQ scores nor GOSE-defined recovery status. Similarly, aTSC rates of change correlated with BTACT rates of change, but not with those of RPQ. Tissue aTSC, previously shown to be diffusely decreased compared to controls at v1, was no longer reduced by v2, suggesting normalization of the sodium ionic equilibrium. These changes were accompanied by marked improvement in outcome. The results support the notion that early aTSC from 23Na MRI predicts future BTACT, but not RPQ scores, nor future GOSE status.

Changes in tissue sodium concentration and sodium relaxation times during the maturation of human knee cartilage: Ex vivo 23 Na MRI study at 10.5 T.

To evaluate the influence of skeletal maturation on sodium (23 Na) MRI relaxation parameters and the accuracy of tissue sodium concentration (TSC) quantification in human knee cartilage. Twelve pediatric knee specimens were imaged with whole-body 10.5 T MRI using a density-adapted 3D radial projection sequence to evaluate 23 Na parameters: B1 + , T1 , biexponential , and TSC. Water, collagen, and sulfated glycosaminoglycan (sGAG) content were calculated from osteochondral biopsies. The TSC was corrected for B1 + , relaxation, and water content. The literature-based TSC (TSCLB ) used previously published values for corrections, whereas the specimen-specific TSC (TSCSP ) used measurements from individual specimens. 23 Na parameters were evaluated in eight cartilage compartments segmented on proton images. Associations between 23 Na parameters, TSCLB - TSCSP difference, biochemical content, and age were determined. From birth to 12 years, cartilage water content decreased by 18%; collagen increased by 59%; and sGAG decreased by 36% (all R2 ≥ 0.557). The short ( ) decreased by 72%, and the signal fraction relaxing with ( ) increased by 55% during the first 5 years but remained relatively stable after that. TSCSP was significantly correlated with sGAG content from biopsies (R2 = 0.739). Depending on age, TSCLB showed higher or lower values than TSCSP . The TSCLB - TSCSP difference was significantly correlated with (R2 = 0.850), (R2 = 0.651), and water content (R2 = 0.738). TSC and relaxation parameters measured with 23 Na MRI provide noninvasive information about changes in sGAG content and collagen matrix during cartilage maturation. Cartilage TSC quantification assuming fixed relaxation may be feasible in children older than 5 years.

The Role of Sodium and Glucose in the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage: A Literature Review of New Evidence

AbstractThe present study aims to review the influence of glycemia and natremia on the propensity to develop complications, worse prognosis, and mortality risk in patients with aneurysmal subarachnoid hemorrhage (aSAH). This is an integrative literature review guided by the guiding question: “Do changes in blood glucose levels or plasma sodium concentration influence in-hospital morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage?”. The search for articles was performed on the PubMed platform, limiting the selection to works published in English in the period from 2017 to 2022. The results found demonstrate that the role of sodium ions in changes in the prognosis of patients is complex, with hypernatremia being the main factor described to worse outcomes. In contrast, the part of hyponatremia is controversial and may not have prognostic value, and serum sodium concentration is increasingly an important item to be evaluated in patients with aSAH. As for glucose, the variability of this substrate, both hyperglycemia and hypoglycemia, may be correlated with in-hospital and long-term mortality in patients with aSAH. Thus, the present study concludes that changes in blood glucose values and plasma sodium concentration influence the in-hospital morbidity and mortality of patients with aSAH. However, it is emphasized that the analysis of the independent influence of each of the related predictors must be done with caution due to the heterogeneity of the results found.

The Utilization of Sodium Concentration in Human Milk from Pump-Dependent Mothers of Preterm Infants as a Measure of Milk Production.

Objective: This study investigated changes in sodium concentrations in human milk from mothers of premature infants using different breast pumps for 14 days postpartum, and the correlation between the sodium concentration in mother's own milk (MOM) and the volume pumped. Study Design: This randomized controlled study recruited 66 mothers of premature infants delivered in our hospital from February to December 2018, and we assigned them to three groups using an envelope method. In intervention group 1, a hospital-grade electric breast pump was used from postpartum day 1 to 14; in intervention group 2, a hospital-grade electric breast pump was used on postpartum days 1 to 5 and a normal personal electric breast pump on postpartum days 6 to 14; in the control group, a personal normal electric breast pump was used from postpartum day 1 to 14. Data recorded included the breast milk volume pumped and milk sodium concentration. Results: The average daily volume of MOM pumped differed statistically (p < 0.05) between the intervention and control groups at postpartum days 7 and 14. The average daily volume pumped did not differ between intervention groups 1 and 2 by postpartum day 14 (p > 0.05). However, the time taken for the sodium concentrations to normalize differed significantly (p < 0.01). At postpartum day 5, the sodium concentrations of 73% of intervention group 1 and 2 mothers were within normal limits, and they were maintained until day 14. In comparison, only 41% of the controls had normal MOM sodium levels on day 5, and they were still high on day 7 in 27.3% of controls. Conclusions: In the early stage of lactation initiation (within 5 days postpartum), using a hospital-grade electric breast pump promotes lactation in mothers who deliver prematurely and the sodium concentrations normalize more quickly. Sodium can be used as an objective biomarker of MOM to evaluate the possibility of delayed lactation in mothers of premature infants, and it could assist interventions in the early postpartum period. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2200061384.

#5069 THE EFFECT OF DIFFERENT DIALYSATE SODIUM CONCENTRATIONS ON AMBULATORY BLOOD PRESSURE AND PULSE WAVE VELOCITY ON HEMODIALYSIS PATIENTS

Abstract Background and Aims Hypertension and arterial stiffness are associated with increased morbidity and mortality in dialysis patients. The purpose of the present study is to investigate the effect of sodium concentration in the dialysate on 72h ambulatory blood pressure and arterial stiffness, as well as its effect on body weight. Method The study involved adult patients on thrice weekly maintenance hemodialysis program. All patients initially underwent six sessions with dialysate sodium concentration of 137 meq/l, subsequently another six sessions with dialysate sodium concentration of 139 meq/l and finally six sessions with dialysate sodium concentration of 141 meq/l. At the start of the sixth hemodialysis session at each different sodium dialysate concentration, the Mobil-o-graph device was placed for 72h in order to cover the 3-day interdialytic interval. The parameters evaluated by the Mobil-o-graph device were peripheral and central systolic (pSBP and cSBP) and diastolic (pDBP and cDBP) blood pressure and pulse wave velocity (PWV). All patients were screened for hydration status with lung ultrasound before entering the study and body weight was actively monitored before each session. Results Overall, 29 patients with a mean age of 57.9±14.9 years were included in this prospective interventional study. Body weight did not change significantly between the 3 dialysate concentrations. There was a significant increase of 6 mmHg in the mean pSBP with the change in sodium concentration from 137 to 139 and to 141 meq/l (from 122.7 to 125,6 and to 128.3 mmHg respectively, p = 0.032). Mean cSBP was also significantly increased by 5 mmHg (from 110.3 to 112.6 and to 115.1 mmHg respectively, p = 0.02). Peripheral and central DBP did not change significantly (from 71.4 to 73.2 and to 74.1 mmHg, p = ns and from 73.9 to 74.8 and to 75.3 mmHg, p = ns, respectively), as well as PWV (from 8.4 to 8.2 cm/sec, p = ns). Conclusion The increasing sodium concentration in the dialysate causes a significant increase in systolic blood pressure and body weight, without a change in PWV.

#6844 MONITOR SWITCHING-INDUCED VARIATIONS IN CONDUCTIVITY AND PLASMA SODIUM DURING HEMODIALYSIS SESSIONS

Abstract Background and Aims Until the advent of the new monitors with sodium modules, the differences between prescribed and actual sodium have been little studied. And most dialysis centers have a fixed sodium prescription. However, the sodium gradient during sessions is one of the key factors in its balance in hemodialysis patients. Predialysis plasma sodium has an important interindividual but not intraindividual variability, which supports the hypothesis of reference sodium (setpoint). This work aimed to compare the impact of switching from the 5008 Cordiax monitor to the new 6008 Cordiax monitor on the actually measured conductivity and initial and final plasma sodium. Method A total of 106 hemodialysis patients were included. Each patient received two dialysis sessions in which only the monitor was varied. The variables collected were: concentrate, prescribed sodium and bicarbonate, real conductivity, initial and final plasma sodium measured by ionic dialysance, and the change in plasma sodium concentration during treatment (ΔPNa), which has been related to mortality when it exceeds 4 mmol/L, was calculated. The clinical research ethics committee of Hospital Clínic de Barcelona approved the present study. Results The change of dialysis monitor showed small, although significant, differences in initial (138.14 mmol/L with 5008 vs. 138.81 mmol/L with 6008) and final plasma sodium (139.58 mmol/L vs. 140.97 mmol/L), as well as in the actual conductivity obtained (13.97 vs. 14.1 mS/cm). The ΔPNa also increased significantly, with the percentage of patients with a ΔPNa greater than 4 mmol/L going from 6 to 22% with the monitor change. All these differences were statistically significant regardless of the concentrate used. All sessions were performed without notable clinical incidents, hypotension, cramps or thirst episodes. Conclusion The ultimate goal of hemodialysis should be to achieve isonatremia that allows complete elimination of interdialytic sodium gain and avoid intradialytic sodium loading. The change from 5008 to 6008 monitor is associated with an increase in conductivity, higher plasma sodium, and an increase in ΔPNa. Knowing and confirming this change will allow us to individualize the sodium prescription to find adequate isonatremic dialysis and, thus, avoid possible adverse effects.

Sodium Magnetic Resonance Imaging Shows Impairment of the Counter-current Multiplication System in Diabetic Mice Kidney.

Sodium magnetic resonance imaging can non-invasively assess sodium distribution, specifically sodium concentration in the countercurrent multiplication system in the kidney, which forms a sodium concentration gradient from the cortex to the medulla, enabling efficient water reabsorption. This study aimed to investigate whether sodium magnetic resonance imaging can detect changes in sodium concentrations under normal conditions in mice and in disease models such as a mouse model with diabetes mellitus. Methods: We performed sodium and proton nuclear magnetic resonance imaging using a 9.4-T vertical standard-bore super-conducting magnet. Results: A condition of deep anesthesia, with widened breath intervals, or furosemide administration in 6-week-old C57BL/6JJcl mice showed a decrease in both tissue sodium concentrations in the medulla and sodium concentration gradients from the cortex to the medulla. Further, sodium magnetic resonance imaging revealed reductions in the sodium concentration of the medulla and in the gradient from the cortex to the medulla in BKS.Cg-Leprdb+/+ Leprdb/Jcl mice at very early type-2 diabetes mellitus stages compared to corresponding control BKS.Cg-m+/m+/Jcl mice. Conclusions: The kidneys of BKS.Cg-Leprdb+/+ Leprdb/Jcl mice aged 6 weeks showed impairments in the countercurrent multiplication system. We propose the utility of 23Na MRI for evaluating functional changes in diabetic kidney disease, not as markers that reflect structural damage. Thus, 23Na MRI may be a potential very early marker for structures beyond the glomerulus; this may prompt intervention with novel efficacious tubule-targeting therapies.

Modeling the heterogeneity of sodium and calcium homeostasis between cortical and hippocampal astrocytes and its impact on bioenergetics.

Emerging evidence indicates that neuronal activity-evoked changes in sodium concentration in astrocytes Na a represent a special form of excitability, which is tightly linked to all other major ions in the astrocyte and extracellular space, as well as to bioenergetics, neurotransmitter uptake, and neurovascular coupling. Recently, one of us reported that Na a transients in the neocortex have a significantly higher amplitude than those in the hippocampus. Based on the extensive data from that study, here we develop a detailed biophysical model to further understand the origin of this heterogeneity and how it affects bioenergetics in the astrocytes. In addition to closely fitting the observed experimental Na a changes under different conditions, our model shows that the heterogeneity in Na a signaling leads to substantial differences in the dynamics of astrocytic Ca2+ signals in the two brain regions, and leaves cortical astrocytes more susceptible to Na+ and Ca2+ overload under metabolic stress. The model also predicts that activity-evoked Na a transients result in significantly larger ATP consumption in cortical astrocytes than in the hippocampus. The difference in ATP consumption is mainly due to the different expression levels of NMDA receptors in the two regions. We confirm predictions from our model experimentally by fluorescence-based measurement of glutamate-induced changes in ATP levels in neocortical and hippocampal astrocytes in the absence and presence of the NMDA receptor's antagonist (2R)-amino-5-phosphonovaleric acid.

Impact of Dapagliflozin Treatment on Serum Sodium Concentrations in Acute Heart Failure

Introduction: The dynamics of serum sodium are important in acute heart failure (AHF), and hyponatremia is associated with a poor prognosis. The effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on serum sodium concentrations in AHF is unknown. Methods: In a single-centre, controlled, randomized study, patients were prescribed dapagliflozin in addition to standard treatment during the first 24 h of hospitalization versus standard treatments. The pre-specified outcome was an absolute change in plasma sodium concentrations between randomization (first 24 h after admission) and discharge. The secondary outcomes were an absolute change in serum sodium concentrations within 48 h of randomization and the persistence of hyponatremia. Results: The sample comprised 285 patients (53% males; average age 73.26 ± 13 years); 140 of these were randomized to the dapagliflozin group. The average ejection fraction was 46 ± 14%; 155 patients (54%) had ischaemic heart failure; and 35% had diabetes mellitus. Median N-terminal pro b-type natriuretic peptide was 4,225 [2,120; 9,105] pg/mL. The average estimated glomerular filtration rate was 53.9 ± 17.2 mL/min. Hospital mortality was 6.7%. At randomization, serum sodium concentrations were 139.8 ± 4.32 mmol/L in the dapagliflozin group versus 140.85 ± 4.04 mmol/L in the control group; p = 0.048. 48 h later, there was an increase in serum sodium in the dapagliflozin group (2 [−2; 4] mmol/L), as compared to the control group (−1 [−3.75; 2]); p < 0.001. This was accompanied by equilibration of the sodium levels between the groups (141.08 ± 4.08 mmol/L in the dapagliflozin group vs. 140.05 ± 4.82 mmol/L in the control group; p = 0.096). At the time of discharge, there was no difference in serum sodium concentrations (140.98 ± 4.77 mmol/L vs. 139.86 ± 4.45 mmol/L; p = 0.082). The increase in serum sodium concentrations during the period of observation [randomization; discharge] was small but statistically significant in the dapagliflozin group (1 [−3; 3.75] mmol/L vs. −2 [−4.5; 2] mmol/L; p = 0.015). Of 36 patients (21 in the dapagliflozin group and 15 in the control group) with baseline hyponatraemia, this persisted in 6 (16.6%) in the dapagliflozin group and in 11 (73.3%) in the control group (p = 0.008). Conclusion: The use of dapagliflozin in AHF is associated with a tendency to the increase in serum sodium concentrations and lesser persistence of hyponatremia. This effect occurred within the first 48 h and persisted until discharge. The impact of dapagliflozin on serum sodium was more pronounced in patients with hyponatremia at randomization.

Nomogram Prediction Model of Hypernatremia on Mortality in Critically Ill Patients

To investigate the value of hypernatremia in the intensive care unit (ICU) for the risk prediction of mortality in severe patients. Clinical data of critically ill patients admitted to the ICU of Beijing Friendship Hospital, were collected for retrospective analysis. Univariate and multivariate logistic regression analyses were employed to analyze the influencing factors. Nomograms predicting the mortality were constructed with R software and validated with repeated sampling. A total of 442 cases were eligible for this study. Hypernatremia within 48 hours of ICU admission, change in sodium concentration (CNa+) within 48 hours, septic shock, APACHE II score, hyperlactatemia within 48 hours, use of continuous renal replacement therapy (CRRT) within 48 hours, and the use of mechanical ventilation (MV) within 48 hours of ICU admission were all identified as independent risk factors for death within 28 days of ICU admission. These predictors were included in a nomogram of 28-day mortality in severe patients, which was constructed using R software. The nomogram could predict the individualized risk of 28-day mortality based on the above factors. The model has better discrimination and accuracy and has high clinical application value.

Cytosolic Sodium Influx in Mesophyll Protoplasts of Arabidopsis thaliana, wt, sos1:1 and nhx1 Differs and Induces Different Calcium Changes.

The sodium influx into the cytosol of mesophyll protoplasts from Arabidopsis thaliana cv. Columbia, wild type, was compared with the influx into sos1-1 and nhx1 genotypes, which lack the Na+/H+ antiporter in the plasma membrane and tonoplast, respectively. Changes in cytosolic sodium and calcium concentrations upon a 100 mM NaCl addition were detected by use of epifluorescence microscopy and the sodium-specific fluorescent dye SBFI, AM, and calcium sensitive Fura 2, AM, respectively. There was a smaller and mainly transient influx of Na+ in the cytosol of the wild type compared with the sos1-1 and nhx1 genotypes, in which the influx lasted for a longer time. Sodium chloride addition to the protoplasts' medium induced a significant increase in cytosolic calcium concentration in the wild type at 1.0 mM external calcium, and to a lesser extent in nhx1, however, it was negligible in the sos1-1 genotype. LiCl inhibited the cytosolic calcium elevation in the wild type. The results suggest that the salt-induced calcium elevation in the cytosol of mesophyll cells depends on an influx from both internal and external stores and occurs in the presence of an intact Na+/H+ antiporter at the plasma membrane. The Arabidopsis SOS1 more effectively regulates sodium homeostasis than NHX1.

Human Milk Sodium and Potassium as Markers of Mastitis in Mothers of Preterm Infants.

Introduction: This prospective longitudinal study examined changes in milk sodium concentration (Na) and sodium:potassium ratio (Na:K), microbiological culture, milk production, and breast health in relation to mastitis after preterm birth. Methods: We studied women who gave birth at 29-34 weeks of gestation in a tertiary obstetric hospital in Perth, Western Australia. Milk samples, 24-hour milk production, and breast health data were collected every second day to day 10 postpartum, then every third day until infant discharge from the neonatal unit. Milk Na and K were measured at point of care (POC) using handheld ion selective meters, and Na:K calculated. Cultures were performed on postnatal days 8, 13, and every 6 days thereafter. For episodes of mastitis, milk was cultured at onset, and Na and Na:K measured daily until resolution. Women were followed up at 4 and 8 weeks postpartum. Results: In a sample of 44 women, 4 mastitis cases were detected in 3 women during their infants' neonatal stay; all had elevated milk Na and Na:K that resolved within 48 hours; 2/4 experienced reduced milk production and 1/4 had heavy growth of Staphylococcus epidermidis. A further 2 mastitis cases were reported in 39 women followed up to 8 weeks postpartum. Four women had elevated milk Na and Na:K without clinical signs of mastitis; three also had reduced milk production. Conclusions: POC testing of milk Na and/or Na:K may offer a useful indicator of breast health. Mastitis may cause an acute reduction in milk production regardless of the presence of culture-positive infection.

MRI of Potassium and Sodium Enables Comprehensive Analysis of Ion Perturbations in Skeletal Muscle Tissue After Eccentric Exercise.

The aims were to investigate if potassium ( 39 K) magnetic resonance imaging (MRI) can be used to analyze changes in the apparent tissue potassium concentration (aTPC) in calf muscle tissue after eccentric exercise and in delayed-onset muscle soreness, and to compare these to corresponding changes in the apparent tissue sodium concentration (aTSC) measured with sodium ( 23 Na) MRI. Fourteen healthy subjects (7 female, 7 male; 25.0 ± 2.8 years) underwent 39 K and 23 Na MRI at a 7 T MR system, as well as 1 H MRI at a 3 T MR system. Magnetic resonance imaging data and blood samples were collected at baseline (t0), directly after performing eccentric exercise (t1) and 48 hours after exercise (t2). Self-reported muscle soreness was evaluated using a 10-cm visual analog scale for pain (0, no pain; 10, worst pain) at t0, t1, and t2. Quantification of aTPC/aTSC was performed after correcting the measured 39 K/ 23 Na signal intensities for partial volume and relaxation effects using 5 external reference phantoms. Edema volume and 1 H T 2 relaxation times were determined based on the 1 H MRI data. Participants were divided according to their increase in creatine kinase (CK) level into high (CK t2 ≥ 10·CK t0 ) and low CK (CK t2 < 10·CK t0 ) subjects. Blood serum CK and edema volume were significantly increased 48 hours after exercise compared with baseline ( P < 0.001). Six participants showed a high increase in blood serum CK level at t2 relative to baseline, whereas 8 participants had only a low to moderate increase in blood serum CK. All participants reported increased muscle soreness both at rest and when climbing stairs at t1 (0.4 ± 0.7; 1.4 ± 1.2) and t2 (1.6 ± 1.4; 4.8 ± 1.9) compared with baseline (0 ± 0; 0 ± 0). Moreover, aTSC was increased at t1 in exercised muscles of all participants (increase by 57% ± 24% in high CK, 73% ± 33% in low CK subjects). Forty-eight hours after training, subjects with high increase in blood serum CK still showed highly increased aTSC (increase by 79% ± 57% compared with t0). In contrast, aTPC at t2 was elevated in exercised muscles of low CK subjects (increase by 19% ± 11% compared with t0), in which aTSC had returned to baseline or below. Overall, aTSC and aTPC showed inverse evolution, with changes in aTSC being approximately twice as high as in aTPC. Our results showed that 39 K MRI is able to detect changes in muscular potassium concentrations caused by eccentric exercise. In combination with 23 Na MRI, this enables a more holistic analysis of tissue ion concentration changes.

Comparison of the efficacy between Del Nido cardioplegia and HTK cardioplegia in Stanford type A aortic dissection patients undergoing open-heart surgery.

Acute Stanford type A aortic dissection is an extremely dangerous and life-threatening cardiovascular disease, usually treated with extracorporeal circulation heart surgery. Histidine-tryptophan-ketoglutarate (HTK) cardioplegia is a protective intracellular myocardial fluid that has been used extensively in different types of extracorporeal circulation surgeries. Del Nido cardioplegia is an extracellular myocardial protection fluid, which was first used in pediatric heart surgery and has been gradually used in a variety of pediatric and adult heart procedures. This study aims to compare the myocardial protection effect between Del Nido and HTK in patients undergoing extracorporeal circulation heart surgery for acute Stanford type A dissection and its impact on patients' prognosis by analyzing selected parameters and clinical manifestations at different time points. Clinical data were collected from 431 patients with acute Stanford type A dissection who were diagnosed and underwent surgery between January 1, 2018 and December 31, 2020 at Xiangya Hospital, Central South University. After excluding some of the data based on exclusion criteria, patients were divided into a HTK group and a Del Nido (DN) group based on type of intraoperative cardioplegia. Propensity score-matching was performed subsequently using the the R statistical software to determine the DN group ( n =40) and HTK group ( n =41). The matching factors were age, sex, hypertension, cardiopulmonary bypass time, and aortic occlusion time. Perioperative data, postoperative complications, blood gas data, and myocardial injury data were collected from the patients, and SPSS 26.0 was used to analyze the data of each group. The DN group had a higher rate of spontaneous cardioversion (41.5% vs 15.0%, P =0.005) and a lower postoperative hospital stay [10.0(8.0,14.0) d vs 13.0(11.0,19.0) d, P <0.05] compared to the HTK group. In terms of changes in blood gas analysis, immediate sodium and potassium concentrations were significantly higher in the DN group than that in the HTK group (both P <0.05). There was no significant difference in myocardial injury indexes between the two groups at different time points (all P >0.05). In terms of postoperative complications, the cardiac complications in DN group were much lower than those in the HTK Group (0 vs 12.5%, P =0.026). Del Nido cardioplegia has similar myocardial protective effects as HTK cardioplegia used in Stanford type A aortic dissection, with a higher rate of cardiac recurrence and fewer cardiac complications. Del Nido cardioplegia should play an important role in future application for acute Stanford type A aortic dissection, but our findings need to be further validated in a large sample of prospective clinical studies.