Hypertonic Saline Infusion Research Articles

FGF-21 levels in polyuria-polydipsia syndrome.

The pathomechanism of primary polydipsia is poorly understood. Recent animal data reported a connection between fibroblast growth factor 21 (FGF-21) and elevated fluid intake independently of hormonal control by the hormone arginine-vasopressin (AVP) and osmotic stimulation. We therefore compared circulating FGF-21 levels in patients with primary polydipsia to patients with AVP deficiency (central diabetes insipidus) and healthy volunteers. In this prospective cohort study, we analyzed FGF-21 levels of 20 patients with primary polydipsia, 20 patients with central diabetes insipidus and 20 healthy volunteers before and after stimulation with hypertonic saline infusion targeting a plasma sodium level ≥150 mmol/L. The primary outcome was the difference in FGF-21 levels between the three groups. Baseline characteristics were similar between the groups except for patients with central diabetes insipidus being heavier. There was no difference in baseline FGF-21 levels between patients with primary polydipsia and healthy volunteers (122 pg/mL (52,277) vs 193 pg/mL (48,301), but higher levels in patients with central diabetes insipidus were observed (306 pg/mL (114,484); P = 0.037). However, this was not confirmed in a multivariate linear regression analysis after adjusting for age, sex, BMI and smoking status. Osmotic stimulation did not affect FGF-21 levels in either group (difference to baseline: primary polydipsia −23 pg/mL (−43, 22); central diabetes insipidus 17 pg/mL (−76, 88); healthy volunteers −6 pg/mL (−68, 22); P = 0.45). To conclude, FGF-21 levels are not increased in patients with primary polydipsia as compared to central diabetes insipidus or healthy volunteers. FGF-21 therefore does not seem to be causal of elevated fluid intake in these patients.

Neural Activation During Tonic Pain and Interaction Between Pain and Emotion in Bipolar Disorder: An fMRI Study.

Objective: Pain and affective disorders have clear clinical relevance; however, very few studies have investigated the association between pain and bipolar disorder. This study investigated the brain activity of patients with bipolar disorder (BPs) undergoing tonic pain and assessed the interaction between pain and emotion.Methods: Ten BPs and ten healthy controls (HCs) were exposed to emotional pictures (positive, neutral, or negative), tonic pain only (pain session), and emotional pictures along with tonic pain (combined session). A moderate tonic pain was induced by the infusion of hypertonic saline (5% NaCl) into the right masseter muscle with a computer-controlled system. Whole-brain blood oxygenation level dependent (BOLD) signals were acquired using 3T functional resonance imaging (fMRI).Results: Ten BPs and ten healthy participants were included in the final analysis. During the pain session, BPs accepted more saline, but showed lower pain rating scores than HCs. When experiencing pain, BPs showed a significant decrease in the BOLD signal in the bilateral insula, left inferior frontal gyrus (IFG), and left cerebellum as compared with HCs. In the combined session, the activated regions for positive mood (pain with positive mood > baseline) in BPs were the left cerebellum, right temporal gyrus, and left occipital gyrus; the activated regions for negative mood (pain with negative mood > baseline) were the right occipital gyrus, left insula, left IFG, and bilateral precentral gyrus.Conclusions: This study presents the preliminary finding of the interaction between pain and emotion in BPs. BPs exhibited lower sensitivity to pain, and the activation of insula and IFG may reflect the interaction between emotion and pain stimulus.

Acute NaCl Loading Reveals a Higher Blood Pressure for a Given Serum Sodium Level in African American Compared to Caucasian Adults.

Purpose: African American individuals are more prone to salt-sensitive hypertension than Caucasian individuals. Small changes in serum sodium (Na+) result in increased blood pressure (BP). However, it remains unclear if there are racial differences in BP responsiveness to increases in serum Na+. Therefore, the purpose of this investigation was to determine if African American adults have altered BP responsiveness to acute changes in serum Na+ compared to Caucasian adults.Methods: We measured beat-by-beat BP, serum Na+, plasma renin activity (PRA), angiotensin II (Ang II), and aldosterone (Aldo) during a 60-min 3% NaCl infusion (hypertonic saline infusion, HSI) in 39 participants (19 African Americans, age: 23 ± 1, 20 Caucasians, age: 25 ± 1). Data reported as African American vs. Caucasian cohort, mean ± SEM.Results: Baseline BP and serum Na+ were similar between groups and increased during HSI in both African American and Caucasian participants (p < 0.01). However, the peak change in serum Na+ was greater in African American participants (Δ5.8 ± 0.34 vs. Δ4.85 ± 0.38 mmol/L, p = 0.03). There was a significant group effect (p = 0.02) and an interaction between race and serum Na+ on systolic BP (p = 0.02). Larger categorical changes in serum Na+ corresponded to changes in systolic BP (p < 0.01) and African American participants demonstrated greater systolic BP responses for a given categorical serum Na+ increase (p < 0.01). Baseline Aldo was lower in African American adults (7.2 ± 0.6 vs. 12.0 ± 1.9 ng/dL, p = 0.03), there was a trend for lower baseline PRA (0.59 ± 0.9 vs. 1.28 ± 0.34 ng/mL/h, p = 0.07), and baseline Ang II was not different (14.2 ± 1.8 vs. 18.5 ± 1.4 pg/mL, p = 0.17). PRA and Aldo decreased during the HSI (p ≤ 0.01), with a greater decline in PRA (Δ–0.31 ± 0.07 vs. Δ–0.85 ± 0.25 ng/mL/h, p < 0.01) and Aldo (Δ–2.5 ± 0.5 vs. Δ–5.0 ± 1.1 ng/dL, p < 0.01) in Caucasian participants. However, the racial difference in PRA (p = 0.57) and Aldo (p = 0.59) reduction were no longer significant following baseline covariate analysis. Conclusion: African American individuals demonstrate augmented serum Na+ to an acute hypertonic saline load and greater systolic BP responsiveness to a given serum Na+. The altered BP response may be attributable to lower basal PRA and Aldo and a subsequently blunted RAAS response during the HSI.

CHANGE OF FUNCTIONAL AND LABORATORY PARAMETERS AFTER COMPENSATION OF ACUTE BLOOD LOSS WITH COOLED HYPERTONIC SOLUTION IN EXPERIMENT

Relevance.High efficiency of hypertonic (hyperosmolar) solutions in acute blood loss is known. However, data on changes in the body, developing as a result of infusion of such drugs (including cooled) in the providing of care after acute blood loss is limited or absent. This fact complicates the development of tactics in their use, especially in emergency situations at low temperatures.Intention.To reveal features of functional and laboratory indicators In experiments on animals as a result of infusion of warm (+22 °С) or the cooled (–3 °С) hypertonic solution based on hydroxyethyl starch and sodium chloride (HyperHAES, further – HHES) at the acute blood loss of 50 % of blood volume (BV).Methodology.Animals (20 male sheep) with modeled blood loss were distributed into 2 experimental and 2 control groups of 5 animals each. Sheep in the 1st experimental group were placed in the heat chamber with temperature –7 °С for 15 min. Then they underwent the intravenous infusion of a cooled HHES at a dose of 4 ml/kg of weight through the jugular vein with a disposable syringe (volume 20 ml) evenly with a speed of 60 ml per minute. After that they were left in the heat chamber until the time of 1 hour in total. Individuals in the 2nd experimental group were injected with an equivalent volume of warm solution during the corresponding periods of the experiment at an external temperature of +22 °C. 1 hour after beginning of the infusion all animals were intravenously injected with colloidal solution based on hydroxyethyl starch (“Voluven”) at an external temperature of +22 °C. During 1 day the dynamics of rectal temperature, arterial pressure, heart rate and respiratory movements, osmolarity of blood plasma and content of osmotically active components, quantitative indicators of red blood were evaluated.Results.Animals at a temperature of +22 °C or at a temperature of –7 °C died in (82 ± 3) min and (70 ± 5) min (p &lt; 0.05) respectively after the start of exfusion. Intravenous fluids (warm or cooled HHES) ensured the survival in 100 % of cases. As a result of blood loss, subsequent infusion of cooled HHES and following presence in the heat chamber, rectal temperature in sheep decreased by 4.9 °C (14.2%, p &lt; 0.05) relative to the initial values. Two and 4 min after infusion of cooled or warm HHES systolic blood pressure increased by 24.9 % (p &lt; 0.05) and 14.9 % (p &lt; 0.05), respectively, and were restored to the normal level during the following 40 min. Infusion of “Voluven” contributed to the stabilization of blood pressure within 1 day after infusion of HHES. Blood loss led to increased heart rate by 2.1 times (p &lt; 0.05), infusion of HHES slightly reduced the severity of tachycardia. Within 10 minutes after the introduction of cooled HHES, dynamics of heart rate was less stable. Infusion of warm or cooled HHES increased osmolarity of blood plasma by 9.5–9.9 % (p &lt; 0.05), which was associated with an increase of sodium and glucose concentrations in blood. Infusion of “Voluven” reduced osmolarity of blood plasma, which became similar to initial values at the end of Day 1 after infusion of HHES. Blood loss, infusion of HHES and “Voluven” decreased quantitative indicators of red blood via removal of red blood cells from the bloodstream, as well as compensatory and post-transfusion hemodilution.Conclusion.The infusion of warm or cold hypertonic saline (HyperHAES) ensures the survival of experimental animals in post-hemorrhagic period. The positive effect of the drug is associated with compensatory haemodilution (including increased osmolarity of blood plasma), as well as with better functioning of the cardiovascular system. Specific cooled HHES effects include an earlier and pronounced rise in blood pressure. Considering changes in functional and laboratory parameters after infusion of warm or cooled HHES, a reliable system should be developed to remove casualties from emergency areas and to take earlier and complete diagnostic and treatment measures.

Approach and management of dysnatremias in cirrhosis.

Hypervolemic (dilutional) hyponatremia is the most common dysnatremia in cirrhosis, with a prevalence close to 50% in patients with ascites, while hypovolemic hyponatremia occurs in a minority of cases. Hyponatremia carries a poor prognosis, being associated with increased mortality and reduced survival after liver transplantation. Hypernatremia is rarer and is also associated with an adverse prognosis. Increased non-osmotic secretion of arginine vasopressin and altered renal tubular sodium handling due to impaired free water generation are the mechanisms leading to hypervolemic hyponatremia, while diuretic-induced fluid loss is the main cause of hypovolemic hyponatremia. Hypernatremia usually follows hypotonic fluid losses due to osmotic diuresis (glycosuria) or lactulose-induced diarrhea. The main clinical manifestations of dysnatremias are due to their effects on the central nervous system: astroglial cell hyperhydration follows hyponatremia-an abnormality that exacerbates ammonia neurotoxicity-while the opposite abnormality occurs with hypernatremia. Asymptomatic or mildly symptomatic hypervolemic hyponatremia is mainly managed by correcting of precipitating factors and non-osmotic fluid restriction. Severe, life-threatening hyponatremia requires hypertonic saline infusion, avoiding rapid and complete correction of serum sodium concentration to prevent neurological sequelae such as osmotic demyelination. V2 receptor blockade by vaptans may be considered in patients with sustained hyponatremia waitlisted for liver transplantation. Diuretic withdrawal and plasma volume expansion are required in hypovolemic hypernatremia. Prompt recognition, removal of the precipitating factor(s) and non-osmotic fluid administration represent the mainstays of hypernatremia management. Rapid correction of long-standing hypernatremia can lead to cerebral edema and has to be avoided.

A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus

BackgroundThe indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin.MethodsFrom 2013 to 2017, we recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked.ResultsA total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test.ConclusionsThe direct measurement of hypertonic saline–stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614.)

Reorganization of motor unit activity at different sites within the human masseter muscle during experimental masseter pain.

The aims were to test the hypotheses that experimental masseter muscle pain leads to recruitment and/or derecruitment of motor units at different sites within the masseter and that the patterns of change in motor unit activity differ between sites. Single motor unit (SMU) activity was recorded at two sites within the right masseter [superior/anterior, inferior/posterior (IP)] during isometric biting tasks (ramp, step level) on an intraoral force transducer in 17 participants during three experimental blocks comprising no infusion (baseline), 5% hypertonic saline infusion (pain), or isotonic saline infusion (control). A visual analog scale (VAS) was used to score pain intensity. The VAS scores were statistically significantly greater during infusion of hypertonic saline than during infusion of isotonic saline. No significant differences in force levels and rates of force change were found between experimental blocks. In comparison with isotonic saline infusion, SMUs could be recruited and derecruited at both sites during hypertonic saline infusion. The frequency of recruitment or derecruitment, in comparison with no change, was statistically significantly greater at the IP site than at the superior/anterior site. Experimental noxious masseter stimulation results in a reorganization of motor unit activity throughout the muscle, and the pattern of reorganization may be different in different regions of the muscle.

Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats

The infusion of hypertonic saline solution (HSS) is known to be beneficial to the treatment of hypovolemic hemorrhage (HH). The central mechanism of HSS-induced cardiovascular and autonomic recovery of animals subjected to HH remains unclear. Hence, the present study evaluated the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats. The wistar rats were subjected to specific lesion of noradrenergic neurons through the nanoinjections of anti-DβH-saporin into caudal ventrolateral medulla (A1 neurons) and nucleus of the solitary tract (A2 neurons). After recovery, mean arterial pressure (MAP) and renal sympathetic nervous activity were recorded. The HH was performed through blood withdrawal until a MAP of 60 mmHg was attained. In sham rats, HSS infusion (3M NaCl) reestablished MAP without change in HH-induced sympathoinhibition. The muscimol (agonist of GABAA receptor) was nanoinjected in MnPO during HH and MnPO inhibition abolished the recovery of MAP and HSS-induced sympathoinhibition. Simultaneous lesions of A1 and A2 abolished MAP restoration and sympathoinhibition after HSS infusion. These results suggest that the recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.

A case series on drug induced hyponatremia: uncommon adverse effect of commonly used drugs

Older patients suffering from depression and psychosis have markedly increased since last decade. So, has the use of antidepressants and antipsychotics. The prevalence of hyponatremia due to these drugs is common in general as well as psychiatric practice. It may also lead to life threatening morbidity and mortality. Loss of renal function, polypharmacy, dementia and other conditions of advanced age can either exacerbate the severity of hyponatremia or mask its onset. In this case series, total four cases were reported of hyponatremia and drugs causing it were escitalopram, quetiapine, tianeptine and oxcarbazepine. Due to polypharmacy, a chance of hyponatremia was more in these patients. Patients received infusion of hypertonic saline with salt added diet to treat hyponatremia. Symptoms of hyponatremia were improved after the treatment. In all four cases, WHO and Naranjo’s causality assessment revealed ‘possible’ causal relationship with the prescribed drug. Prescribers should be aware of such adverse effect due to these drugs.

Effect of infusion speed of 7.5% hypertonic saline on brain edema in patients with craniocerebral injury: An experimental study

This study firstly used a rat traumatic brain injury model to compare the therapeutic effects of different intravenous infusion speed of 7.5% hypertonic saline (HS). Then the authors applied different delivery rate of 7.5% HS to two groups of patients to figure out the optimal infusion rates. A total of 100 rats were randomly divided into control group, group A (7.5% HS 6 mL/h), group B (7.5% HS 3 mL/h), and group C (7.5% HS 2 mL/h). All rats were established for the brain injury model. A total of 30 patients were selected and randomly divided into group A (250 mL/h) and group B (125 mL/h), with 15 cases in each group. Urine amount was recorded per hour; furthermore, blood was extracted from the patients to measure the levels of AQP4, NKCC1, tumour necrosis factor-α (TNF-a), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Compared with other groups, the expression levels of NKCC1 and AQP4 mRNA in group A was the lowest (P < 0.05). NKCC1 and AQP4 protein expression levels were the lowest in all the groups (P < 0.05). On the aspect of patients, group A displayed more significant difference compared with B group in terms of AQP4, NKCC1, TNF-a, IL-1β, and IL-6 (P < 0.05). In the two groups, a significant difference was noted in the urine amount at 4 h after administration (P < 0.05). In our study, infusion of hypertonic saline (250 mL/h) at the optimal rate of 7.5% HS decreased the intracranial pressure, brain tissue edema, and inflammatory cytokine expression; moreover, it can promote brain tissue protection.

The effects of audiovisual distraction on the muscle sympathetic responses to experimental muscle pain.

Pain elicited by intramuscular infusion of hypertonic saline solution causes muscle sympathetic nerve activity (MSNA) to increase in some subjects, yet decrease in others. Although the direction of the response is not predictable based on baseline physiological and psychological parameters, we know that it results from sustained functional changes in specific brain regions that are responsible for the behavioral and cardiovascular responses to psychological stressors, as well as those involved in attention. The aim of this study was to investigate whether MSNA responses to experimental muscle pain in humans could be altered with an audiovisual stimulus that served to distract them from the pain. MSNA was recorded from the left common peroneal nerve of 20 young healthy individuals during a 45-min intramuscular infusion of hypertonic saline solution into the ipsilateral tibialis anterior muscle. The distracting stimulus commenced 15min after the start of the infusion and lasted for 15min. Fifteen subjects showed an increase in mean burst amplitude of MSNA (to 176.4 ± 7.9% of baseline), while five showed a decrease (to 73.1 ± 5.2% of baseline); distraction had no effect on these profiles. These results indicate that even though the subjects were attending to the audiovisual stimulus, and were presumably distracted from the pain, it failed to alter the MSNA responses to muscle pain.

Hypertonic saline infusion affects glycemic responses following glucose load in healthy men

Low water intake and plasma hypertonicity have been independently associated with hyperglycemia and incidence of diabetes mellitus in epidemiological studies. Recent data also suggest that reducing water intake deteriorates glucose regulation in patients with type 2 diabetes. To date, it is unclear whether plasma hypertonicity would also impact glycemic control in subjects with normal glycemic and insulinemic function.OBJECTIVETo assess the effect of hypertonic saline infusion on glycemic responses to an oral glucose tolerance test (OGTT) in healthy adult men.METHODS30 healthy, non‐smoking adult men (36.6±7.0 y, 83.9±12.8 kg, body mass index 27.0±3.4 kg·m−2, HbA1c 5.2±0.3%, HOMA‐IR 1.59±0.97) were recruited for this study. Each subject underwent two experimental trials, consisting of a 2‐h intravenous infusion of saline (ISO: 0.9% NaCl and HYPER: 3.0% NaCl) at an infusion rate of 0.1 ml·kg·min−1, followed by a 4‐h oral OGTT. Blood samples were taken at 30 min intervals throughout the infusion period and during the OGTT. Plasma osmolality (POsm), glucose (Glu), angiotensin II (AngII), renin, and aldosterone (Ald) were measured and plasma volume (PV) was calculated using hematocrit and hemoglobin based on the Dill &amp; Costill equation.RESULTSPOsm at baseline was similar between conditions (287±3 and 286±3 mmol·kg−1 in HYPER and ISO, respectively). Following the 2‐h infusion, POsm was significantly higher in the HYPER condition than the ISO condition (305‐±3 vs. 288±3 mmol·kg−1; P &lt; 0.0001), with greater PV expansion (20.1±6.9 vs. 10.9±3.2%, P &lt; 0.0001). In the HYPER condition, POsm remained above baseline throughout the OGTT (296±3 mmol·kg−1 at OGTT4‐h; P &lt; 0.0001). During the OGTT, Glu in the HYPER trial was higher than in the ISO trial at 60 min (HYPER: 157±24; ISO: 145±29 mg·dL−1; P &lt; 0.018) and 90 min (HYPER: 139±33; ISO 128±29 mg·dL−1; P &lt; 0.038). The renin‐angiotensin‐aldosterone system was suppressed as indicated by decreased plasma values of AngII, renin, and Ald, probably due to PV expansion in both trials.CONCLUSIONPlasma hypertonicity induced by hypertonic saline infusion unfavorably affected glycemic response to an OGTT in healthy adult men.Support or Funding InformationThis research was supported by Danone ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Copeptin Responses to Isotonic and Hypertonic Saline Infusion in Healthy Adults

Copeptin, a c‐terminal segment of arginine vasopressin (AVP) prohormone, has equimolar secretion to AVP in response to osmotic, stress‐related, and hemodynamic stimulation. For this reason, and because of the difficulties in measuring AVP directly linked to its short half‐life, copeptin has been used as a stable and sensitive surrogate marker for AVP for various clinical indications. However, the plasma copeptin response to osmotic stimulation remains poorly documented.PURPOSEExamine the plasma copeptin response to plasma hyperosmolality induced by hypertonic saline infusion.METHODSSixty healthy adults (50% male, age: 30±1 y, weight: 78.2±15.2 kg, body mass index: 26.9±4.0 kg·m−2) were infused intravenously with 3% (HYPER) or 0.9% (ISO) NaCl for 2 h (0.1 ml·kg−1·min−1) in a counterbalanced, cross‐over design. Blood samples were collected every 30 minutes. Plasma osmolality (POsm), copeptin (PCop; BRAHAMS copeptin proAVP, Thermo Fisher Scientific, Germany), and sodium (PNa) were measured, and changes in plasma volume (PV) were calculated from hematocrit and hemoglobin using the Dill &amp; Costill equation.RESULTSFollowing the HYPER trial, PNa increased from 136±2 mmol ·L−1 to 146.5±3 mmol ·l−1 (P &lt; 0.001), with PV expansion of 18.7±7.3% (P &lt; 0.001). Both POsm and PCop increased significantly (0 min: 286±3 mmol·kg−1 and 4.5±3.7 pmol·L−1; 120 min: 305±4 mmol·kg−1 and 20.4±12.8 pmol·L−1, respectively, P &lt; 0.001). Mean (95% CI) PCop increased with increasing POsm: 3.2 (2.5–3.8) pmol·L−1 for POsm ≤ 284.9 mmol·kg−1; 5.4 (3.8–7.0) pmol·L−1 for POsm 285–289.9; 6.2 (4.3–8.0) pmol·L−1 for POsm 290–294.9; 8.5 (7.1–9.9) pmol·L−1 for POsm 295–299.9; 12.3 (10.2–14.4) pmol·L−1 for POsm 300–304.9; and 19.2 (16.3–22.2) pmol·L−1 for POsm ≥ 305 mmol·kg−1. In contrast, during the ISO trial PNa remained unchanged during the 2‐h infusion (135.9±1.9 vs. 137.6±1.6 mmol·L−1), while PV expanded by 10.5±4.4% (P &lt; 0.001 compared to baseline; P &lt; 0.001 compared to HYPER). Neither POsm (0 min: 285±4,120 min: 287±3 mmol·kg−1) nor PCop (0 min: 4.1±1.8, 120 min: 3.8±3.0 pmol·L−1) were affected during the ISO trial.CONCLUSIONPlasma copeptin was stimulated by increased plasma osmolality during a hypertonic infusion.Support or Funding InformationThis research was supported by Danone ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Assessment of Cardiac Function of Rbm 20−/− Rats Using Pressure‐Volume Loop Analysis After 28 Days of Angiotensin II Treatment

RNA binding motif 20 (Rbm20), a muscle specific splicing factor for the sarcomeric protein titin, affects diastolic and systolic properties of the heart per the Frank‐Starling mechanism. Failure to alter titin expression from the predominant fetal isoform N2BA to the shorter, adult N2B isoform in Rbm20−/− (KO) rats, results in impaired cardiomyocyte relaxation, increased compliance of the ventricular walls, and dilated cardiomyopathy. These pathologies are similar to those seen in humans with this mutation, which often results in early, sudden death in both species. Angiotensin II (AII) acutely causes vasoconstriction, and chronically results in cardiac hypertrophy, characterized by an increase in cardiac wall stiffness. We hypothesized that 28 days of treatment with AII would increase the stiffness of the myocardium, resulting in improved cardiac function in KO rats. KO rats and age‐matched wild type (WT) controls were fitted with subdermal osmotic pumps, delivering AII continuously (0.25 μL·hr −1) for 28 days. After AII exposure, cardiac function was assessed in vivo using pressure‐volume loop analysis. Under isoflurane anesthesia, loops were recorded under baseline, brief inferior vena cava occlusion, and hypertonic saline infusion (20–40 μL) conditions. The rat was then heparinized, and blood collected for cuvette calibration. No group differences (p&lt;0.05) were found in cardiac output (23.3±0.8 KO; 26.9±2.5 mL·min−1 WT), heart rate (295±21 KO; 341±16 b·min−1 WT), and stroke volume (80.8±9.1 KO; 79.5±7.6 μL WT). However, significant reductions were found in contractility (preload recruitable stroke work; 41.6±10.8 KO; 86.9±8.2 mmHg WT), stroke work (5.13±0.73; 8.13±0.86 mmHg·min WT), and ejection fraction (49.8±4.2 KO; 74.7±7.4 % WT) in KO rats. KO rats were able to maintain stroke volume, despite impaired contractility, due to a significant increase in preload (169±16 KO; 113±7 μL WT) and decrease in afterload (84.4±8.7 KO; 113±9 mmHg WT). We conclude that KO rats failed to improve contractility with 28 days of AII treatment, but maintained normal cardiac output through compensatory changes in preload and afterload.Support or Funding InformationThis project is supported in part by a grant from the National Institute of General Medical Sciences (2P20GM103432) from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Does hypertonic saline infusion with furosemide improve outcomes for patients with acute CHF exacerbation?

Does hypertonic saline infusion with furosemide improve outcomes for patients with acute CHF exacerbation?

Therapeutic Advances in Hyponatremia: Fluids, Diuretics, Vaptans, and More

Background: Hyponatremia is frequently encountered in geriatric patients and is associated with significant morbidity and mortality. Traditional management approaches have targeted underlying causes—such as volume repletion with normal saline in dehydrated patients, loop diuretics and fluid restriction in hypervolemic patients, and fluid restriction and salt tablets in euvolemic patients. Elderly patients are at particular risk of hypovolemic hyponatremia because of dehydration, as well as the syndrome of inappropriate antidiuretic hormone. In addition to fluid restriction, syndrome of inappropriate antidiuretic hormone may be treated with demeclocycline, lithium, and urea, although these agents are limited by side effects. Loop diuretics are standard therapy for hyponatremia in congestive heart failure, cirrhosis, or nephrotic syndrome; although these agents, and to a greater extent thiazide diuretics, can cause hyponatremia and should be used cautiously. In severe hyponatremia, standard therapy is the infusion of hypertonic (3%) saline. Judicious monitoring is paramount, as rapid overcorrection is associated with central pontine myelinolysis. Areas of Uncertainty: Although these therapies are well established, the gravity of improper sodium correction has led to uncertainty and varying dosing strategies. Hypertonic saline infusion rates may be weight based or standardized and can be used concurrently with deamino-delta-d-arginine vasopressin. As well, loop diuretics vary considerably in metabolism and half-life, and choice of agent may have implications for mortality in congestive heart failure. Finally, even the simple strategy of fluid restriction may not apply to patients with highly concentrated urine. Therapeutic Advances: Unresolved questions around treatment of hyponatremia have spurred development of newer therapeutics, notably arginine vasopressin receptor blockers or vaptans, which have been shown to be effective in the treatment of euvolemic and hypervolemic chronic hyponatremia. In 2 randomized, double-blind, placebo-controlled multicenter trials (SALT-1 and SALT-2), tolvaptan significantly increased serum sodium at days 4 and 30 in 448 patients with mean baseline serum sodium 129 meq/L. Furthermore, vaptans can cause liver damage, and the FDA has cautioned against their use in patients with underlying liver disease. The cost of vaptans has been a major barrier, but this may be offset by decreases in length of stay in hospitalized patients. Conclusions: Vaptans have shown promise in the treatment of euvolemic and hypervolemic chronic hyponatremia but have not shown long-term mortality benefits.

The Effects of Experimental Temporalis Muscle Pain on Jaw Muscle Electromyographic Activity During Jaw Movements and Relationships with Some Psychological Variables

To determine if the effects of experimental temporalis muscle pain on jaw muscle activity vary with the jaw task performed, jaw displacement magnitude, participant being studied, and with psychological measures. Jaw movement was tracked, and electromyographic (EMG) activity was recorded from the masseter and anterior temporalis and digastric muscles in 14 asymptomatic participants during standardized opening/closing jaw movement, free chewing, and standardized chewing tasks. Tasks were repeated in three blocks: Block 1 (baseline), Block 2 (during 5% hypertonic or 0.9% isotonic saline infusion into the anterior temporalis), and Block 3 (during infusion of the opposite solution). Participants also completed the Depression, Anxiety, and Stress Scales 21 (DASS 21), the Fear of Pain Questionnaire (FPQ III), the Pain Self-Efficacy Questionnaire (PSEQ), and the Pain Catastrophizing Scale (PCS). Analyses involved linear mixed-model analysis and Pearson correlations. P < .05 was considered statistically significant. The presence of a significant difference in jaw muscle EMG activity between hypertonic and isotonic saline infusions varied between tasks and between jaw muscle agonists and antagonists, but not in displacement magnitude. There were qualitative differences between participants in the effects of infusion on EMG activity. During hypertonic saline infusion, significant positive correlations were noted between jaw-closing EMG activity and anxiety, fear of medical pain, and PCS scores. Noxious stimulation of the temporalis muscle results in changes in jaw muscle activity, which can vary with the task, the muscle, the participant, and some psychological variables.

The influence of acute elevations in plasma osmolality and serum sodium on sympathetic outflow and blood pressure responses to exercise.

Elevated plasma osmolality (pOsm) has been shown to increase resting sympathetic nerve activity in animals and humans. The present study tested the hypothesis that increases in pOsm and serum sodium (sNa+) concentration would exaggerate muscle sympathetic nerve activity (MSNA) and blood pressure (BP) responses to handgrip (HG) exercise and postexercise ischemia (PEI). BP and MSNA were measured during HG followed by PEI before and after a 23-min hypertonic saline infusion (HSI-3% NaCl). Eighteen participants (age 23 ± 1 yr; BMI 24 ± 1 kg/m2) completed the protocol; pOsm and sNa+ increased from pre- to post-HSI (285 ± 1 to 291 ± 1 mosmol/kg H2O; 138.2 ± 0.3 to 141.3 ± 0.4 mM; P < 0.05 for both). Resting mean BP (90 ± 2 vs. 92 ± 1 mmHg) and MSNA (11 ± 2 vs. 15 ± 2 bursts/min) were increased pre- to post-HSI ( P < 0.05 for both). Mean BP responses to HG (106 ± 2 vs. 111 ± 2 mmHg, P < 0.05) and PEI (102 ± 2 vs. 107 ± 2 mmHg, P < 0.05) were higher post-HSI. Similarly, MSNA during HG (20 ± 2 vs. 29 ± 2 bursts/min, P < 0.05) and PEI (19 ± 2 vs. 24 ± 3 bursts/min, P < 0.05) were greater post-HSI. In addition, the change in MSNA was greater post-HSI during HG (Δ9 ± 2 vs. Δ13 ± 3 bursts/min, P < 0.05). A second set of participants ( n = 13, age 23 ± 1 yr; BMI 24 ± 1 kg/m2) completed a time control (TC) protocol consisting of quiet rest instead of an infusion. The TC condition yielded no change in resting sNa+, pOsm, mean BP, or MSNA (all P > 0.05); responses to HG and PEI were not different pre- to post-quiet rest ( P > 0.05). In summary, acutely increasing pOsm and sNa+ exaggerates BP and MSNA responses during HG exercise and PEI. NEW & NOTEWORTHY Elevated plasma osmolality has been shown to increase resting sympathetic activity and blood pressure. This study provides evidence that acute elevations in plasma osmolality and serum sodium exaggerated muscle sympathetic nerve activity and blood pressure responses during exercise pressor reflex activation in healthy young adults.

Serum sodium response to hypertonic saline infusion therapy in traumatic brain injury

Serum sodium response to hypertonic saline infusion therapy in traumatic brain injury

Copeptin during hypertonic saline infusion in a polyuria/polydipsia syndrome case series

Copeptin during hypertonic saline infusion in a polyuria/polydipsia syndrome case series