Changes In Plasma Osmolality Research Articles

Plama Osmolality Status in Acute Stroke Patients and in Healthy Individuals in Rajshahi Medical College Hospital

Background: Stroke is the most prevalent neurological emergency and accounts for approximately 50% of all neurological disorders in medical college hospitals. It is the leading cause of adult neurological morbidity and the third leading cause of death globally. Changes in plasma osmolality are associated with increased complications, mortality, morbidity, and disability in stroke patients. Objective: This study aims to investigate the changes in plasma osmolality in different types of acute stroke patients and its impact on stroke outcomes. Method: The study included two groups: Group I comprised 104 acute stroke patients (mean age 58.87±13.70) as cases, and Group II consisted of 104 age- and sex-matched healthy individuals (mean age 57.55±12.60) as controls. Each stroke patient underwent cranial computed tomography within the first 24 hours. Blood tests for blood sugar, serum electrolytes, lipid profile, and blood urea were performed. The CT findings and pathological test results were analyzed using SPSS software. Result: Among the 104 stroke patients, 71 (68.27%) had ischemic stroke, and 33 (31.73%) had hemorrhagic stroke. Dyselectrolytaemia was observed in 73 (70.20%) of the stroke patients, while 31 (29.80%) had normal electrolyte levels. Hyperosmolality was present in 58 (55.77%) of the patients, and hypoosmolality was found in 3 (2.88%). Conclusions: Abnormal plasma osmolality is a significant independent risk factor for complications in acute stroke patients, both ischemic and hemorrhagic. Plasma osmolality estimation should be considered a crucial clinical investigation for evaluating acute stroke patients in the early stages.

Rates of osmoconformation in triploid eastern oysters, and comparison to their diploid half-siblings

Triploid eastern oysters (Crassostrea virginica) suffer greater mortalities than diploids in the U.S. Gulf of Mexico estuaries when extreme low salinities (< 5) and elevated temperatures (≥ 28 °C) coincide. To investigate potential causes, changes in plasma osmolality, hemolymph pH, valve opening and mortality in diploid and triploid oyster half-siblings were compared during a step-down gradual acclimation from a salinity of 5 to 1 (5, 2.5, 2.0, 1.5, 1.0) at 23 °C (expt 1) and at 28 °C (expt 2). To further explore differences in diploid and triploid oyster responses to changing salinity, we compared their plasma osmolality after abrupt decreases in salinity from 20 to 10 and 5, followed by increases in salinity from 5 and 10 to 20 once oysters had osmoconformed to the lowered salinities (expt 3). Lastly, changes in wet weights of mantle tissue explants were compared between diploid and triploid oysters every 10 min for 40 min after being transferred from a salinity of 20 to 10 (expt 4). Oysters of both ploidies were able to osmoconform to water at salinities between 5 and 1.5. After a decrease in salinity, triploid oysters were slower to open their valves and osmoconform, were less efficient in maintaining acid-base status enduring longer periods of acidic hemolymph pH, and were less efficient in regulating tissue water content compared to half-sibling diploid oysters. At a salinity of 1.0, plasma of both diploid and triploid oysters remained hyperosmotic, their hemolymph acidic and their valves closed. Oysters osmoconformed faster at 28 °C than at 23 °C, but the combination of low salinity (≤ 1.5) and higher temperature caused rapid mortalities regardless of ploidies. Triploid oysters, however, started dying earlier and at greater percentages when salinity of 1.5 and temperature of 28 °C were combined. Triploids have been embraced as a means to support higher production, but results indicate superimposed stressors, such as low salinity and high temperature, may be more lethal to triploid than diploid oysters.

Effect of thyroxine on Na+/K+-ATPase and SDH activities in gills and kidney during osmotic adjustments of Heteropneustes fossilis at higher salinity

Aim: The aim of the present study was to investigate the facilitatory role of thyroxine during adaptation process of catfish, Heteropneustes fossilis in higher salinity following its exogenous administration by monitoring changes in plasma osmolality, branchial and renal sodium-potassium dependent adenosine triphosphatase and succinic dehydrogenase enzyme activity profiles and study the effect of direct transfer of fish to higher salinities on plasma thyroxine levels. Methodology: Catfish were directly transferred from tap water to 30 and 35% sea water and plasma thyroxine profiles were analysed. Fish were injected with thyroxine at a dose of 2 and 5 µg g-1 b.wt. daily for five days and then transferred to tap water and 30% sea water. Fish were sampled after day 3 and day 6, post-transfer and plasma osmolality was measured, and the enzyme activities were determined in gills and kidney. Results: Higher levels of plasma thyroxine were observed after transfer of fish from tap water to higher salinities. Treatment of fish with thyroxine at higher dose (5 µg g-1 b.wt.) showed a significant increase in plasma osmolality in tap water (p&lt;0.05) while the enzymes in gills were found to be significantly higher both in tap water (p&lt;0.05; p&lt;0.01for Na+/K+-ATPase and p&lt;0.001 for SDH) and 30% sea water (p&lt;0.001for Na+/K+-ATPase and p&lt;0.01; p&lt;0.001 for SDH). No significant changes were observed in any of the parameters analysed after exogenous administration of thyroxine at lower dose (2 µg g-1 b.wt.). Interpretation: Thyroxine affects the osmotic adjustment of fish following transfer to higher salinities and its exogenous administration at at a dose of 5 µg g-1 b.wt. may improve the hypoosmoregulatory ability. Key words: Hormonal control, Osmoregulation, Teleost, Thyroid hormones

Volume replacement is associated with a diminished osmolar effect of mannitol in patients with acute brain injury

IntroductionAnimal experiments recently demonstrated that replacing urinary loses with crystalloid diminishes the therapeutic effect of mannitol by reducing the increase in osmolality. We aimed to investigate whether this effect is similarly seen in in brain-injured patients by studying the association between total body fluid balance (TBB) and the osmolar response to mannitol. MethodsWe performed a retrospective cohort study of adult patients with acute brain injury between 2015 and 2021 who received ≥ 2 doses of mannitol within 8 hours and no intercurrent concentrated saline solution. We analyzed the association between the change in TBB (∆TBB) and change in osmolality (∆Osm) before and after mannitol in a linear model, both as univariate and after adjustment for common confounding factors. ResultsOf 6,145 patients who received mannitol, 155 patients met inclusion criteria (mean age 60 ± 17 years, 48% male, 83% white). The mean total mannitol dose was 2 ± 0.5 g/kg and the mean change in plasma osmolality was 7.9 ± 7.1 mOsm/kg. Each 1 L increase in ∆TBB was associated with a change of -1.1 mOsm/L in ∆Osm (95% CI [-2.2, -0.02], p = 0.045). The magnitude of association was similar to that of total mannitol dose and remained consistent in an adjusted model and after excluding outliers. ConclusionsIn patients with acute brain injury, a positive TBB is associated with a diminished mannitol-induced increase in plasma osmolality. Future prospective studies are needed to confirm these findings and their influence on the therapeutic effect of mannitol.

An update review on hemodynamic instability in renal replacement therapy patients.

Hemodynamic instability in patients undergoing kidney replacement therapy (KRT) is one of the most common and essential factors influencing mortality, morbidity, and the quality of life in this patient population. Decreased cardiac preload, reduced systemic vascular resistance, redistribution of fluids, fluid overload, inflammatory factors, and changes in plasma osmolality have all been implicated in the pathophysiology of hemodynamic instability associated with KRT. A cascade of these detrimental mechanisms may ultimately cause intra-dialytic hypotension, reduced tissue perfusion, and impaired kidney rehabilitation. Multiple parameters, including dialysate composition, temperature, posture during dialysis sessions, physical activity, fluid administrations, dialysis timing, and specific pharmacologic agents, have been studied as possible management modalities. Nevertheless, a clear consensus is not reached. This review includes a thorough investigation of the literature on hemodynamic instability in KRT patients, providing insight on interventions that may potentially minimize factors leading to hemodynamic instability.

Postpartum Hypernatremia with Extrapontine Rhabdomyelinolysis: A Case Report.

Hypernatremia (serum sodium>160 meq/L) present with diverse neurological manifestations, ranging from flaccid paralysis to impaired cognition, encephalopathy, and even deep coma. Osmotic demyelination refers to changes in brain cells because of an acute change in plasma osmolality. It is further divided into two types, i.e., central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM). Patients with EPM, besides spasticity, may also present with other movement disorders such as catatonia, parkinsonism, and dystonia. We present a case of a postpartum woman bought to the emergency department by her relatives in an unconscious state. In view of poor sensorium (Glasgow coma scale < 7), she was intubated and received mechanical ventilatory support. On admission, computed tomography ofthebrain was normal, and the patient was transferred to the intensive care unit (ICU) for further management. The preliminary work-up in the ICU showed hypernatremia (serum sodium of 182 mEq/L) with hyper-osmolality (359 mOsm/kgH2O). She was managed as per the ICU protocol for hypernatremia. During her ICU stay, her sensorium improved, but she developed flaccid paralysis and was quadriplegic. Thus, a tracheostomy was performed, and she was weaned from the ventilator. After ventilator weaning, she was transferred to the ward for further rehabilitation. During rehabilitation, the patient was able to sit and takefoodorally.To date, only a few cases are reported in postpartum women with acute severe hypernatremia caused by high-grade fever and loss of body fluids leading to extra-pontine demyelination and flaccid paralysis. This case highlightsthat prompt recognition and appropriate intervention can improve the outcomes in these patients.

Exercise-Induced Hyponatremia: An Assessment of the International Hydration Recommendations Followed During the Gran Trail De Peñalara and Vitoria-Gasteiz Ironman Competitions.

IntroductionHyponatremia often occurs during the practice of endurance sports. We evaluated the impact on hyponatremia of the hydration recommendations of the Third International Exercise-Associated Hyponatremia Consensus Development Conference 2015 (3IE-AHCD) during the 2017 Gran Trail de Peñalara marathon (GTP) and the Vitoria Gasteiz Ironman triathlon (VGI).MethodsProspective study of GTP and VGI athletes participating in four information sessions in the months prior to the events, to explain that hydration should only be according to their level of thirst, per the recommendations of the 3IE-AHCD. Consenting event finishers were included in final analysis. Pre- and post-race anthropometric and biochemical parameters were compared.ResultsThirty-six GTP (33 male) and 94 VGI (88 male) finishers were evaluated. GTP race median fluid intake was 800 ml/h, with 900 ml/h in the VGI race. 83.3% GTPfin and 77.6% VGIfin remained eunatremic (blood sodium 135–145 mmol/L). Only 1/36 GTP and 1/94 VGI participant finished in hyponatremia, both with a sodium level of 134 mmol/L. Fourteen percent of GTP, and 21.2% of VGI participants finished in hypernatremia, with no increase in race completion times. No participating athlete required medical attention, except for musculoskeletal complaints. Pro-BNP and Copeptin levels rose significantly. Changes in copeptin levels did not correlate with changes in plasma osmolality, nor total body water content in impedance analysis.ConclusionsRecommending that athletes' fluid intake in endurance events be a function of their thirst almost entirely prevented development of hyponatremia, without induction of clinically significant hypernatremia, or a negative repercussion on race completion times.

Arginine vasopressin-Venus reporter mice as a tool for studying magnocellular arginine vasopressin neurons

Arginine vasopressin (AVP) synthesized in the magnocellular neurons of the hypothalamus is transported through their axons and released from the posterior pituitary into the systemic circulation to act as an antidiuretic hormone. AVP synthesis and release are precisely regulated by changes in plasma osmolality. Magnocellular AVP neurons receive innervation from osmosensory and sodium-sensing neurons, but previous studies showed that AVP neurons per se are osmosensitive as well. In the current study, we made AVP-Venus reporter mice and showed that Venus was expressed exclusively in AVP neurons and was upregulated under water deprivation. In hypothalamic organotypic cultures from the AVP-Venus mice, Venus-labeled AVP neurons in the supraoptic and paraventricular nuclei survived for 1 month, and Venus expression was upregulated by forskolin. Furthermore, in dissociated Venus-labeled magnocellular neurons, treatment with NaCl, but not with mannitol, decreased Venus fluorescence in the soma of the AVP neurons. Thus, Venus expression in AVP-Venus transgenic mice, as well as in primary cultures, faithfully showed the properties of intrinsic AVP expression. These findings indicate that AVP-Venus mice as well as the primary hypothalamic cultures could be useful for studying magnocellular AVP neurons.

Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons.

SummaryMisfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER.

Changes in fluid and acid-base status of diarrheic calves on different oral rehydration regimens

The administration of oral rehydration solutions (ORS) is an effective method to treat dehydration and acidosis in calves suffering from diarrhea. The ORS can be prepared in water or milk. The aim of the present study was to elucidate how fluid and acid-base balance change after feeding milk compared with ORS prepared in water or milk to diarrheic calves. Calves (n = 30) with naturally acquired diarrhea were sequentially assigned in a 2:1 ratio to the following pretreatments: milk and water-ORS (pretreatment 1; n = 20 calves) or milk-ORS (pretreatment 2; n = 10 calves), respectively. The assignment was done on the day of diarrhea diagnosis. On d 3 ± 1 following assignment to pretreatment group, and after a fasting period of 9 h, diarrheic calves were subjected to the following treatments: 2 L of milk (pretreatment 1; n = 10 calves), water-ORS (pretreatment 1; n = 10 calves), or milk-ORS (pretreatment 2; n = 10 calves). Blood samples were taken before and at several time points until 6 h after feeding. Plasma protein, osmolality, and electrolytes were determined and a blood gas analysis was performed. Change in plasma volume was calculated according to plasma protein, and water intake during the experimental period was recorded. Plasma volume was increased 30 min after feeding water-ORS or milk but the increase was less pronounced after feeding milk compared with water-ORS. After feeding milk-ORS, no significant increase in plasma volume could be detected. Because of the pretreatment, plasma osmolality was higher in calves fed milk-ORS, but no change in plasma osmolality after feeding was detected. No difference in water consumption between the treatment groups was noted within the observed 6-h period. The pH was increased after feeding milk-ORS, whereas water-ORS and milk-feeding did not increase pH in blood. Pretreatment with milk-ORS resulted in higher baseline d-lactate concentration, but feeding milk-ORS reduced d-lactate values after feeding. In calves with diarrhea, plasma volume increased more quickly and to a greater extent after feeding water-ORS; thus, we recommend treating diarrheic calves with water-ORS before supplying milk. Nevertheless, diarrheic calves need milk to fulfill their energy needs. The administration of ORS in milk combined with free water access is more advisable than feeding milk exclusively because milk has no alkalinizing ability and contains less sodium. However, the effects of milk-ORS feeding on d-lactate levels in diarrheic calves need further elucidation.

Ion-regulation, acid/base-balance, kidney function, and effects of hypoxia in coho salmon, Oncorhynchus kisutch, after long-term acclimation to different salinities

Land-based salmon farming in closed containment recirculation aquaculture systems (RAS) is an emerging industry with the potential for reducing disease prevalence, improving production efficiency, and reducing environmental impacts compared with open net-pen aquaculture. Salinity and oxygen levels are environmental factors that have significant impacts on the physiology of fishes and possibly influence the production efficiency of fishes in aquaculture. These parameters are particularly relevant for fish production in RAS, where most water parameters can be manipulated and tightly controlled. While much is known about the specific mechanisms associated with the acute transfer between FW and SW and the reverse, little is known about the effects of long-term acclimation on ion- and acid/base-regulation, especially at intermediate salinities. We measured gas-exchange, ion-regulation, acid/base balance, and renal function in coho salmon (Oncorhynchus kisutch Walbaum, 1792) acclimated to four salinities (2.5, 5.0, 10, and 30 ppt) for over a year in RAS and investigated how animals prioritize these functions when faced with 24 h exposure to hypoxia (PO2 = 63 mmHg = 8.4 kPa = 3.76–4.48 mg l−1). We show that fish that were long-term acclimated to 30 ppt had substantially higher plasma osmolality and [Na+] than fish acclimated to lower salinities. These changes were associated with a marked reduction in blood pH at 30 ppt relative to 2.5 ppt, and we discuss a possible thermodynamic link between salinity acclimation and acid/base regulation. Further, we show that hypoxia exposure results in changes in plasma osmolality by over 80 mOsm kg−1, but only in 30 ppt water, demonstrating a salinity-dependent trade-off between gas exchange and osmoregulation. This study provides insight into the physiological state and hypoxia sensitivity of market sized salmon reared under industry-relevant conditions in RAS.

Plasma Hyperosmolality Prolongs QTc Interval and Increases Risk for Atrial Fibrillation in Traumatic Brain Injury Patients.

Introduction: Hyperosmotic therapy with mannitol is frequently used for treatment cerebral edema, and 320 mOsm/kg H2O has been recommended as a high limit for therapeutic plasma osmolality. However, plasma hyperosmolality may impair cardiac function, increasing the risk of cardiac events. The aim of this study was to analyze the relation between changes in plasma osmolality and electrocardiographic variables and cardiac arrhythmia in patients treated for isolated traumatic brain injury (iTBI). Methods: Adult iTBI patients requiring mannitol infusion following cerebral edema, and with a Glasgow Coma Score below 8, were included. Plasma osmolality was measured with Osmometr 800 CLG. Spatial QRS-T angle (spQRS-T), corrected QT interval (QTc) and STJ segment were calculated from digital resting 12-lead ECGs and analyzed in relation to four levels of plasma osmolality: (A) <280 mOsm/kg H2O; (B) 280–295 mOsm/kg H2O; (C) 295–310 mOsm/kg H2O; and (D) >310 mOsm/kg H2O. All parameters were measured during five consecutive days of treatment. Results: 94 patients aged 18-64 were studied. Increased plasma osmolality correlated with prolonged QTc (p < 0.001), intensified disorders in STJ and increased the risk for cardiac arrhythmia. Moreover, plasma osmolality >313 mOms/kg H2O significantly increased the risk of QTc prolongation >500 ms. Conclusion: In patients treated for iTBI, excessively increased plasma osmolality contributes to electrocardiographic disorders including prolonged QTc, while also correlating with increased risk for cardiac arrhythmias.

P2517Feasibility and safety of cardiac rehabilitation program during Ramadan fasting among patients having coronary artery disease and moderate left ventricular dysfunction

Abstract Background Ramadan fasting (RF) is an important worship activity for Muslims. It entails complete abstinence of food and fluids from dawn to sunset (14–16 hours) for 30 days. The safety and feasibility cardiac rehabilitation program during (RF) is largely unknown. Aim To assess safety and feasibility of cardiac rehabilitation program (CRP) during (RF) in patients with coronary artery disease (CAD) with moderate left ventricular dysfunction (LVD). Moreover, to study the effect of (RF) on some blood parameters Patients and methods Fifty three patients joining (CRP) at our university hospital were included in the study. All had (CAD) with moderate (LVD). Patients were divided into two groups according to their Ramadan fasting status. Group I (fasting) were 32, while group II (non fasting) were 21. All patients underwent exercise training during cardiac rehabilitation in Ramadan. Serum lipid profile, plasma osmolality, renal functions, echocardiography and exercise parameters were assessed before and after (CRP).Clinical follow up was available for one month post Ramadan. Results The two groups were similar in baseline characteristics including: risk factors, serum osmolality, urea, creatinine, lipid profile, hemoglobin values, ejection fraction and exercise parameters.All patients successfully completed the (CRP). No patient in group I had any ischemic episode or exacerbation of (LVD) during or one month after the end of Ramadan.After the program, both groups showed significant improvement in ejection fraction (group I: 43±2% to 52±2%, p&lt;0.001, group II: 41.1±4 to 47.2±3%. p&lt;0.002), total cholesterol (group I: 174.8±40.8 to 169.4±37.1 mg%, p=0.034, group II: 172.9±43.3 to 163.0±40.7 mg%, p=0.01), LDL: Group I: 100.7±33.4 to 94.5±261 mg%, p=0.023, group II: 104.5±42.1 to 93.8±33.8 mg%, p=0.005), and HDL: Group I: 42.7±10.6 to 44.5±10.9 mg%, p=0.029, group II: 40.6±8 to 45±8.9 mg%, p&lt;0.001). However, triglyceride levels improved significantly only in group I (162.3±65.4 to 152.8±52.3 mg%, p=0.042, group II: 144±60 to 133.9±48.8 mg%, p=0.149) l. There was also similar improvement in exercise duration after (CRP) in both groups. It is worthy to note that fasting did not increase the serum osmolality in group I (277.91±15.14 before, and 281.01±11.61 mmol/L after (RF), p value= 0.34) Conclusion Cardiac rehabilitation is feasible and safe among patients with (CAD) and (LVD) during (RF). Moreover, (RF) resulted in significant improvement in serum triglycerides without change in plasma osmolality denoting absence of hemoconcentration despite fasting.

Monitoring transcellular fluid shifts during episodes of intradialytic hypotension using bioimpedance spectroscopy.

BackgroundTranscellular fluid shifts during dialysis treatment could be related to the frequency and severity of intradialytic hypotension (IDH). We investigated that (i) in addition to ultrafiltration, extracellular fluid (ECF) is further depleted by transcellular fluid shifts and (ii) changes in intracellular fluid (ICF), which have been overlooked so far, or if they were considered, are not understood, might be due to these fluid shifts.MethodsThirty-six patients were categorized as haemodynamically stable, asymptomatic IDH or unstable (symptomatic IDH) according to their changes in systolic blood pressure and associated clinical symptoms. Their intradialytic changes in body fluids were studied using bioimpedance spectroscopy measurements and compared among groups.ResultsFor IDH-prone patients, data showed a rapid drop in ECF that was more than expected from the ultrafiltration rate (UFR) profile and was associated with a significant increase in ICF (P = 0.001). Study of accumulative loss profiles of ECF revealed a loss in ECF up to 300 ml, more than that predicted from UFR for unstable patients.ConclusionsThe considerable discrepancy between the expected and measured loss in ECF might provide evidence of transcellular fluid shifts possibly induced by changes in plasma osmolarity due to haemodialysis. Moreover, the results suggest a pattern of fluid removal in IDH-prone patients that significantly differs from that in haemodynamically stable patients.

Rattlesnakes Must Drink: Meal Consumption Does Not Improve Hydration State.

Water is critical to survival, yet free-standing water is often rare in deserts and seasonally dry environments. Thus, many dry-adapted species utilize either metabolic (that produced from metabolism) or dietary (that found in food) water to meet their hydric needs. It is suspected that desert reptiles can fulfill their hydric needs solely through dietary water intake. However, food consumption does not improve the hydration state of Gila monsters (Heloderma suspectum), a binge-feeding desert lizard, and meal consumption by snakes leads to increased voluntary drinking. Therefore, we predicted that meal consumption would not improve hydration state in dehydrated western diamondbacked rattlesnakes (Crotalus atrox). We found no significant difference in the change in plasma osmolality between moderately dehydrated snakes that consumed a meal and those that did not. In fact, snakes that received a meal reached severe dehydration more than a week sooner than snakes that did not receive a meal. Additionally, consuming a meal when severely dehydrated did not reduce plasma osmolality, whereas severely dehydrated snakes provided with water ab lib. returned to a normosmotic state. These results provide the most convincing evidence that carnivorous desert reptiles likely rely on free-standing water to fulfill their hydric needs. These species have thus had to adapt to sporadic water availability through minimizing water loss and tolerating considerable variation in plasma osmolality.

Is increased plasma TMAO a compensatory response to hydrostatic and osmotic stress in cardiovascular diseases?

Recent clinical studies show a positive correlation between elevated plasma TMAO and increased cardiovascular risk. However, the mechanism of the increase and biological effects of TMAO in the circulatory system are obscure.Plasma TMAO level depends mostly on the following three factors. First, the liver produces TMAO from TMA, a gut bacteria metabolite of dietary choline and carnitine. Second, plasma TMAO increases after ingestion of dietary TMAO from fish and seafood. Finally, plasma TMAO depends on TMAO and TMA excretion by the kidneys.Ample evidence highlights protective functions of TMAO, including the stabilization of proteins and cells exposed to hydrostatic and osmotic stresses, for example in fish exposed to hydrostatic stress (deep water) and osmotic stress (salty water).Osmotic stress and hydrostatic stresses are augmented in cardiovascular diseases such as hypertension. In hypertensive subjects a diastole-systole change in hydrostatic pressure in the heart may exceed 220 mmHg with a frequency of 60–220/min. This produces environment in which hydrostatic pressure changes over 100,000 times per 24 h. Furthermore, cardiovascular diseases are associated with disturbances in water-electrolyte balance which produce changes in plasma osmolarity. Perhaps, the increase in plasma TMAO in cardiovascular diseases is analogous to increased level of plasma natriuretic peptide B, which is both a cardiovascular risk marker and a compensatory response producing beneficial effects for pressure/volume overloaded heart. In this regard, there is some evidence that a moderate increase in plasma TMAO due to TMAO supplementation may be beneficial in animal model of hypertension-related heart failure. Finally, increased plasma TMAO is present in humans consuming seafood-rich diet which is thought to be health-beneficial.We hypothesize that increased plasma TMAO serves as a compensatory response mechanism which protects cells from hydrostatic and osmotic stresses.

2343-PUB: Reduction of HbA1c after SGLT2 Inhibitors Correlate with Change in Plasma Osmolarity but Not with Elevation of Hematocrit in Japanese Patients with Type 2 Diabetes

Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors is expected its hematopoietic effect for treatment of the anemia in chronic renal failure. However, it is still unclear whether the effect is independent from its antidiabetic effect. In this study, we investigated correlations between hematocrit elevation, HbA1c reduction or parameters reflecting diuretic change in patients with type 2 diabetes (T2D). A total of 46 patients (male: n = 33, age: 54.6 ± 10.4 [mean ± SD] years, BMI: 29.2 ± 4.3 kg/m2, HbA1c: 8.7 ± 1.0%) with T2D who were newly administered SGLT2 inhibitors from July 2014 to November 2016 were retrospectively identified. The patients with HbA1c less than 7.0% at the baseline or who showed decrease in hematocrit or increase in HbA1c were excluded. Changes in HbA1c, hematocrit, urine specific gravity, uric acid, serum creatinine and plasma osmolarity levels between before and 30 days after the administration of the drugs were evaluated. Plasma osmolarity was calculated by the formula (2 x (Na [mEq/l] + K [mEq/l])) + (BUN [mg/dl]/2.8) + (glucose [mg/dl]/18). HbA1c was decreased (-0.68 ± 0.50%; p = 0.001) and hematocrit (2.1 ± 1.4%; p = 0.002) and urine specific gravity (0.008 ± 0.009 g/ml; p &amp;lt; 0.001) were increased significantly. However, uric acid, serum creatinine and plasma osmolarity did not show change. Changes in HbA1c and plasma osmolarity showed significant correlation (r = -0.31; p = 0.03) whereas changes in hematocrit and plasma osmolarity did not (r = -0.01; p = 0.94). HbA1c showed no significant correlation with hematocrit, serum creatinine, uric acid or urine specific gravity; hematocrit also did not have significant correlation with serum creatinine, uric acid or urine specific gravity. In conclusion, our data suggest that the elevation of hematocrit and decrease in HbA1c after the administration of SGLT2 inhibitors have different relation with parameters reflecting diuretic effects. Disclosure Y. Wada: None. Y. Hamamoto: Speaker’s Bureau; Self; Novo Nordisk A/S. Y. Nakatani: None. J. Fujikawa: None. Y. Iwasaki: None. S. Yoshiji: None. M. Aizawa-Abe: None. K. Iwasaki: None. S. Honjo: None. A. Hamasaki: None.

Hypertonic Mannitol for the Prevention of Intradialytic Hypotension: A Randomized Controlled Trial

Intradialytic hypotension (IDH) is a common complication at the initiation of hemodialysis (HD) therapy, is associated with greater mortality, and may be related to relatively rapid shifts in plasma osmolality. This study sought to evaluate the effect of an intervention to minimize intradialytic changes in plasma osmolality on the occurrence of IDH. Double-blind, single-center, randomized, controlled trial. Individuals requiring initiation of HD for acute or chronic kidney disease. Mannitol, 0.25g/kg/h, versus a similar volume of 0.9% saline solution during the first 3 HD sessions. The primary end point was average decline in systolic blood pressure (SBP). The secondary end point was the proportion of total sessions complicated by IDH (defined as a decrease≥ 20mm Hg from the pre-HD SBP). Exploratory end points included biomarkers of cardiac and kidney injury. 52 patients were randomly assigned and contributed to 156 study visits. There were no significant differences in average SBP decline between the mannitol and placebo groups (15±11 vs 19±16mm Hg; P= 0.3). The proportion of total sessions complicated by IDH was lower in the mannitol group compared to placebo (25% vs 43%), with a nominally lower risk for developing an episode of IDH (OR, 0.38; 95% CI, 0.14-1.00), though this finding was of borderline statistical significance (P= 0.05). There were no consistent differences in cardiac and kidney injury biomarker levels between treatment groups. Modest sample size and number of events. In this pilot randomized controlled trial studying patients requiring initiation of HD, we found no difference in absolute SBP decline between those who received mannitol and those who received saline solution. However, there were fewer overall IDH events and a nominally lower risk for dialysis sessions being complicated by IDH in the mannitol group. A larger multicenter randomized controlled trial is warranted. Government funding to an author (Dr Mc Causland is supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK102511). Registered at ClinicalTrials.gov with study number NCT01520207.

Transient receptor potential vanilloid type 4 is expressed in vasopressinergic neurons within the magnocellular subdivision of the rat paraventricular nucleus of the hypothalamus

Changes in plasma osmolality can drive changes in the output from brain centres known to control cardiovascular homeostasis, such as the paraventricular nucleus of the hypothalamus (PVN). Within the PVN hypotonicity reduces the firing rate of parvocellular neurons, a neuronal pool known to be involved in modulating sympathetic vasomotor tone. Also present in the PVN is the transient receptor potential vanilloid type 4 (TRPV4) ion channel. Activation of TRPV4 within the PVN mimics the reduction in firing rate of the parvocellular neurons but it is unknown if these neurons express the channel. We used neuronal tracing and immunohistochemistry to investigate which neurons expressed the TRPV4 ion channel protein and its relationship with neurons known to play a role in plasma volume regulation. Spinally projecting preautonomic neurons within the PVN were labelled after spinal cord injection of FluoroGold (FG). This was followed by immunolabelling with anti‐TRPV4 antibody in combination with either anti‐oxytocin (OXT) or anti‐vasopressin (AVP). The TRPV4 ion channel was expressed on 63% of the vasopressinergic magnocellular neurosecretory cells found predominantly within the posterior magnocellular division of the PVN. Oxytocinergic neurons and FG labelled preautonomic neurons were present in the same location, but were distinct from the TRPV4/vasopressin expressing neurons. Vasopressinergic neurons within the supraoptic nucleus (SON) were also found to express TRPV4 and the fibres extending between the SON and PVN. In conclusion within the PVN, TRPV4 is well placed to respond to changes in osmolality by regulating vasopressin secretion, which in turn influences sympathetic output via preautonomic neurons.

Cardiopulmonary bypass prime composition: beyond crystalloids versus colloids.

In the literature addressing cardiopulmonary bypass (CPB) prime composition, there is a considerable lack of discussion concerning plasma osmolality changes induced by using a hyperosmolar prime. With this study, we try to determine the magnitude and temporal relationship of plasma osmolality changes related to the use of a hyperosmolar CPB prime. In this prospective observational study performed in a university hospital setting, we enrolled thirty patients scheduled for elective coronary bypass surgery. Plasma osmolality was analysed on eight occasions. A hyperosmolar CPB prime was used. Analyses of the perioperative plasma osmolality on eight occasions gave the following results: the preoperative osmolality level was normal (297±4 mOsm/kg); a significant increase to 322±17 mOsm/kg (p<0.001) was observed at the commencement of CPB and remained elevated after 30 minutes (310±4 mOsm/kg) and throughout the procedure (309±4 mOsm/kg); the osmolality level returned to 291±5 mOsm/kg on day 1 postoperatively and remained normal the following day (291±6 mOsm/kg). Use of hyperosmolar CPB prime resulted in a dramatic and instant elevation of the plasma osmolality. Rapid changes in plasma osmolality are associated with organ dysfunction (e.g. osmotic demyelination syndrome), therefore, effects on plasma osmolality related to the CPB prime composition should be recognised. Influence on organ function and clinical outcome warrants further investigations. - Clinical Trials.gov (NCT03060824). Changes in Plasma Osmolality Related to the Use of Cardiopulmonary Bypass With Hyperosmolar Prime. URL: https://clinicaltrials.gov/ct2/show/NCT03060824?term=cpb&cond=osmolality&rank=1.