Decrease In Plasma Sodium Research Articles

CYP11B2 inhibitor dexfadrostat phosphate suppresses the aldosterone-to-renin ratio, an indicator of sodium retention, in healthy volunteers.

High aldosterone is a key driver of hypertension and long-term negative sequelae. We evaluated the safety and efficacy of dexfadrostat phosphate (DP13), a novel aldosterone synthase (CYP11B2) inhibitor, in healthy participants. This randomized, double-blind, placebo-controlled study was conducted in two parts. In part A, a single-ascending dose escalation, 16 participants received oral DP13 1-16 mg. Part B was a multiple-ascending dose, sequential group study in which 32 participants received oral DP13 4, 8 or 16 mg once daily for 8 days. Safety and tolerability were monitored throughout. An adrenocorticotropic hormone (ACTH) stimulation test at maximal blood drug concentrations defined the dose range for multiple dosing. DP13 was well tolerated at all doses, with no serious adverse events. In part B, all DP13 doses (4, 8 and 16 mg) over 8 days effectively suppressed aldosterone production, increased the urinary sodium/potassium ratio, decreased plasma sodium and increased plasma potassium and renin levels compared with placebo, resulting in potent suppression of the aldosterone-to-renin ratio (ARR). Endocrine counter-regulation resulted in the 4 mg dose no longer sustaining 24-h aldosterone suppression after 8 days of treatment, unlike the 8- and 16 mg doses. There was no evidence of drug-induced adrenal insufficiency (ACTH stress challenge). In patients with excess aldosterone and ensuing sodium retention driving hypertension, managing sodium balance is critical. A CYP11B2 inhibitor like DP13, whose effectiveness can be monitored by a reduction in ARR, may prove valuable in managing aldosterone-dependent hypertension and primary aldosteronism.

Hyponatremia at the onset of necrotizing enterocolitis is associated with intestinal surgery and higher mortality

It has previously been shown that hyponatremia reflects the severity of inflammation in pediatric gastrointestinal diseases. Interpretation of electrolyte disorders is a common, but not well studied challenge in neonatology, especially in the context of early detection of necrotizing enterocolitis and bowel necrosis. The aim of this study was to assess if hyponatremia, or a decrease in plasma sodium level, at the onset of necrotizing enterocolitis (NEC) is associated with intestinal ischemia/necrosis requiring bowel resection and/or NEC-related deaths. This was a retrospective cohort study including patients with verified NEC (Bell’s stage ≥ 2) during the period 2009–2014. Data on plasma sodium 1–3 days before and at the onset of NEC were collected. The exposure was hyponatremia, defined as plasma sodium < 135 mmol/L and a decrease in plasma sodium. Primary outcome was severe NEC, defined as need for intestinal resection due to intestinal ischemia/necrosis and/or NEC-related death within 2 weeks of the onset of NEC. Generalized linear models were applied to analyze the primary outcome and presented as odds ratio. A total of 88 patients with verified NEC were included. Fifty-four (60%) of them had severe NEC. Hyponatremia and a decrease in plasma sodium at onset of NEC were associated with increased odds of severe NEC (OR crude 3.91, 95% CI (1.52–10.04) and 1.19, 95% CI (1.07–1.33), respectively). Also, a sub-analysis, excluding infants with pneumoperitoneum during the NEC episode, showed an increased odds ratio for severe NEC in infants with hyponatremia (OR 23.0, 95% CI (2.78–190.08)).Conclusions: The findings of hyponatremia and/or a sudden decrease in plasma sodium at the onset of NEC are associated with intestinal surgery or death within 2 weeks.What is Known:• Clinical deterioration, despite optimal medical treatment, is a relative indication for surgery in infants with necrotizing enterocolitis.• Hyponatremia is a common condition in preterm infants from the second week of life.What is New:• Hyponatremia and a decrease in plasma sodium level at the onset of necrotizing enterocolitis are positively associated with need of surgery or death within 2 weeks.• In infants with necrotizing enterocolitis, without pneumoperitoneum, where clinical deterioration despite optimal medical treatment is the only indication for surgery, hyponatremia, or a decrease in plasma sodium level can predict the severity of the disease.

Exercise-Associated Hyponatremia in Endurance Performance

Exercise-Associated Hyponatremia in Endurance Performance Abstract. Exercise-associated hyponatremia is defined as a plasma sodium concentration of <135 mmol/l and was first described by Timothy Noakes at the Comrades Marathon in South Africa in the mid-1980s. A decrease in plasma sodium <135 mmol/l occurs with excessive fluid intake. Risk factors include long to very long endurance performance, extreme climatic conditions, female gender and competitions in the USA. Regarding its prevalence by sport, exercise-associated hyponatraemia tends to occur while swimming and running, but rarely when cycling. While mild exercise-associated hyponatremia does not lead to clinical symptoms, severe hyponatremia due to cerebral edema can lead to neurological deficits and even death. The best prevention of exercise-associated hyponatremia is the reduction of fluid intake during exercise.

Osmoregulation Performance and Kidney Transplant Outcome.

Kidney transplant recipients have an impaired ability to dilute urine but seldom develop baseline hyponatremia before ESRD. Although hyponatremia is a risk factor for adverse events in CKD and in kidney transplant recipients, it remains unclear whether subtler alterations in osmoregulation performance are associated with outcome. We studied a single-center prospective cohort of 1258 kidney transplant recipients who underwent a water-loading test 3 months after transplant to determine osmoregulation performance. Measured GFR (mGFR) was performed at the same visit. A group of 164 healthy candidates for kidney donation served as controls. We further evaluated the association of osmoregulation performance with transplantation outcomes and subsequent kidney function. Unlike controls, most kidney transplant recipients failed to maintain plasma sodium during water loading (plasma sodium slope of -0.6±0.4 mmol/L per hour in transplant recipients versus -0.12±0.3 mmol/L per hour in controls; P<0.001). Steeper plasma sodium reduction during the test independently associated with the composite outcome of all-cause mortality and allograft loss (hazard ratio [HR], 1.73 per 1 mmol/L per hour decrease in plasma sodium; 95% confidence interval [95% CI], 1.23 to 2.45; P=0.002) and allograft loss alone (HR, 2.04 per 1 mmol/L per hour decrease in plasma sodium; 95% CI, 1.19 to 3.51; P=0.01). The association remained significant in a prespecified sensitivity analysis excluding patients with hyperglycemia. In addition, a steeper plasma sodium slope 3 months after transplantation independently correlated with lower mGFR at 12 months (β=1.93; 95% CI, 0.46 to 3.41; P=0.01). Reduced osmoregulation performance occurs frequently in kidney transplant recipients and is an independent predictor of renal outcome.

Thiazide-induced hyponatraemia is associated with increased water intake and impaired urea-mediated water excretion at low plasma antidiuretic hormone and urine aquaporin-2

Hyponatraemia is a common, potentially life-threatening, complication of thiazide diuretics. The mechanism of thiazide-induced hyponatraemia is incompletely understood. Previous experiments have suggested a direct effect of thiazide diuretics on the plasma membrane expression of aquaporin (AQP)2. We examined the effects of a single re-exposure to hydrochlorothiazide (HCTZ) 50 mg on water balance, renal sodium handling and osmoregulation in 15 elderly hypertensive patients with a history of thiazide-induced hyponatraemia and 15 matched hypertensive controls using thiazide diuretics without previous hyponatraemia. Patients with thiazide-induced hyponatraemia had significantly lower body weight and lower plasma sodium and osmolality at baseline. After HCTZ administration, plasma sodium and osmolality significantly decreased and remained lower in patients compared with controls (P < 0.001). Plasma antidiuretic hormone (ADH) and urine AQP2 were low or suppressed in patients, whereas solute and electrolyte-free water clearance was significantly increased compared with controls. Ad libitum water intake was significantly higher in patients (2543 ± 925 ml) than in controls (1828 ± 624 ml, P < 0.05), whereas urinary sodium excretion did not differ. In contrast, urea excretion remained significantly lower in patients (263 ± 69 mmol per 24 h) compared with controls (333 ± 97 mmol per 24 h, P < 0.05) and predicted the decrease in plasma sodium following HCTZ administration. Thiazide diuretics are associated with markedly impaired free water excretion at low ADH and AQP2 in elderly patients. The higher water intake and lower urea excretion in patients points to an important role for polydipsia and urea-mediated water excretion in the pathogenesis of thiazide-induced hyponatraemia.

Impact of Gnetum africanum and Amaranthus rectroflexus Plant Food on Urea, Creatinine and Plasma Electrolytes

Amaranthus rectroflexus (AmE) and Gnetum africanum (GnA) is the most popular green leafy vegetable in Gabon and is gaining equal popularity as a delicious food leaf in other African countries such as Cameroon, Nigeria, Congo and Angola. The purpose of this study was to assess the impact of these plants in modulating urea, creatinine and plasma electrolytes. 50 mg/kg of aqueous extract were given to rats in the experimental groups for two week, while rats in the control group received an appropriate volume of water. Urea creatinine, and Plasma electrolytes were measured by spectrophotometric method. Chronic oral administration for two week of 50 mg/kg of AmE and GnA aqueous extracts significantly decreased plasma sodium concentration benefit to potassium (P 0.05) in weight, blood glucose, creatinine and urea plasma concentration.

Analysis of risk factors for acute kidney injury in patients with decompensated cirrhosis

To investigate the risk factors for and the prognosis of acute kidney injury (AKI) in decompensated cirrhotic patients. A total of 126 patients with decompensated cirrhosis and with (n =60) or without (n =66, control group) AKI were enrolled in this retrospective analysis. Follow-up was carried out on all patients, with durations ranging from less than 1 year to up to 4 years. Blood biochemistry, liver and renal functional parameters and prognosis of these patients were recorded. Logistic regression analysis was used to evaluate possible risk factors for decompensated cirrhotic patients developing AKI. The patients with AKI had a significantly lower survival rate than the patients without AKI (55.0% vs.83.3%, x2 =13.270, p =0.001). Unconditional multivariate logistic regression analysis identified risk factors of AKI development in decompensated cirrhotic patients as increased serum creatinine (odds ratio (OR):1034), increased total bilirubin (OR:1.005), increased international normalized ratio (INR; OR:2.471), decreased plasma sodium concentration (OR:0.910), decreased serum cholinesterase (OR:0.999), and decreased glomerular filtration rate (GFR; OR:0.972) (all P less than 0.05). The development of acute kidney injury represents an adverse prognosis in decompensated cirrhotic patients. An increase in serum creatinine, total bilirubin or INR or a decrease in plasma sodium concentration, serum cholinesterase or GFR may be early-warning factors of development of AKI in decompensated cirrhotic patients.

Host Stress Response Is Important for the Pathogenesis of the Deadly Amphibian Disease, Chytridiomycosis, in Litoria caerulea

Chytridiomycosis, a disease caused by Batrachochytrium dendrobatidis, has contributed to worldwide amphibian population declines; however, the pathogenesis of this disease is still somewhat unclear. Previous studies suggest that infection disrupts cutaneous sodium transport, which leads to hyponatremia and cardiac failure. However, infection is also correlated with unexplained effects on appetite, skin shedding, and white blood cell profiles. Glucocorticoid hormones may be the biochemical connection between these disparate effects, because they regulate ion homeostasis and can also influence appetite, skin shedding, and white blood cells. During a laboratory outbreak of B. dendrobatidis in Australian Green Tree Frogs, Litoria caerulea, we compared frogs showing clinical signs of chytridiomycosis to infected frogs showing no signs of disease and determined that diseased frogs had elevated baseline corticosterone, decreased plasma sodium and potassium, and altered WBC profiles. Diseased frogs also showed evidence of poorer body condition and elevated metabolic rates compared with frogs showing no signs of disease. Prior to displaying signs of disease, we also observed changes in appetite, body mass, and the presence of shed skin associated with infected but not yet diseased frogs. Collectively, these results suggest that elevated baseline corticosterone is associated with chytridiomycosis and correlates with some of the deleterious effects observed during disease development.

Letter to the Editor

Dear Editor:I read with great interest the recent article by Anastasiou CA, Kavouras SA, Arnaoutis G, et al (and supported by the Gatorade Sport Science Institute) entitled “Sodium Replacement and Plasma Sodium Drop During Exercise in the Heat When Fluid Intake Matches Fluid Loss” (J Athl Train. 2009;44(2):117–123). In this letter, I propose further discussion and an alternative interpretation of their findings.A purpose of the study was to examine the ability of several beverages (high [Na+], low [Na+], placebo, and distilled water) to maintain serum sodium concentrations when fluid supplementation matched fluid lost to sweating. The authors concluded that even small amounts of sodium (19 mmol/L) in replenished fluid were able to prevent the decrease in plasma sodium observed when sodium-free fluids were ingested during prolonged exercise. An alternative interpretation of the results is that sodium-containing beverages better attenuated the drop in serum [Na+] during prolonged exercise in a state of overhydration.In citing Greenleaf and Sargent's seminal 1965 work,1 the authors noted that “thirst perception is an insufficient means to match fluid losses during exercise.” This is true, although the goal of exactly matching fluid losses during exercise is unclear. It is well established that exercising humans replace a fraction (20%–70%) of sweat losses when given ad libitum access to fluids.2–4 Recent work has demonstrated maintenance of total body water despite weight loss of 4%–5% during the prolonged exercise of an ultradistance triathlon.5 The correlation with body-weight loss and maintenance of physiologic [Na+] is well established.6 Sharwood et al7 demonstrated that large losses of body weight in an ultradistance triathlon correlated with neither decreased performance nor likelihood of presenting to medical stations. The recommendation to replace all weight loss with fluid volume is not supported by these studies.The authors also noted that the findings of their study, along with those of Vrijens and Rehrer,8 contrast with those of several other investigators9–11 as to the ability of sodium-containing fluids to maintain plasma volume and [Na+]. The difference is to be found in the methods: in the latter 3 studies, ad libitum hydration was offered to participants, whereas in the former 2, participants were overhydrated by replacing sweat losses.The authors concluded that “when sweating is excessive and the goal is to restore fluid losses during exercise, special attention should be paid to the replenishment of sodium.” The data presented indicate that the goal of rehydration during exercise is not to replenish fluid losses but rather to maintain [Na+]. This is best accomplished by drinking to thirst,12–16 does not require sodium supplementation,9,17 and is usually accompanied by mild to moderate weight loss.6 It is my hope that critical review of hydration, as presented in this letter, will influence more runners to avoid the complications associated with overhydration.

Disturbed Homeostasis in Sodium-Restricted Mice Heterozygous and Homozygous for Aldosterone Synthase Gene Disruption

We have determined that differences in expression of aldosterone synthase (AS) affect responses to a low-salt diet. In AS-null mice (AS(-/-)), but not in wild-type, low salt significantly decreased plasma sodium and increased potassium. The increased urine volume (1.5xwild-type) and decreased urine osmolality (0.7xwild-type), present in AS(-/-) mice on normal salt, became more severe (2.3xwild-type and 0.5xwild-type) on low salt, but neither changed in wild-type. In both genotypes, plasma vasopressin was similar on normal and low salt, and desmopressin injection significantly increased urine osmolality. Renal mRNA levels for aquaporin 1 and 3 were unchanged by genotype or diet and epithelial sodium channel and Na(+)-K(+)-2Cl(-)-cotransporter by genotype. In AS(-/-) mice, aquaporin 2 mRNA increased on normal salt, whereas Na(+)Cl(-)-cotransporter and cortex K(+) channel mRNAs decreased on both diets. The low blood pressure of AS(-/-) mice was decreased further by low salt, despite additional increases in renin, intrarenal arterial wall thickness, and macula densa cyclogenase-2 mRNA. In AS(+/-) mice on normal salt, adrenal AS mRNA was slightly decreased (0.7xwild-type), but blood pressure was normal. On low salt, their blood pressure was less than wild-type (101+/-2 mm Hg versus 106+/-2 mm Hg), even though renin mRNA increased to 2xwild-type. We conclude that aldosterone is critical for urine concentration and maintenance of blood pressure and even a mild reduction of AS expression makes blood pressure sensitive to low salt, suggesting that genetic differences of AS levels in humans may influence how blood pressure responds to dietary salt.

What can be concluded regarding water versus sports drinks from the Vrijens-Reher experiments?

This study assessed whether replacing sweat losses with sodium-free fluid can lower the plasma sodium concentration and thereby precipitate the development of hyponatremia. Ten male endurance athletes participated in one 1-h exercise pretrial to estimate fluid needs and two 3-h experimental trials on a cycle ergometer at 55% of maximum O2 consumption at 34°C and 65% relative humidity. In the experimental trials, fluid loss was replaced by distilled water (W) or a sodium-containing (18 mmol/l) sports drink, Gatorade (G). Six subjects did not complete 3 h in trial W, and four did not complete 3 h in trial G. The rate of change in plasma sodium concentration in all subjects, regardless of exercise time completed, was greater with W than with G (−2.48 ± 2.25 vs. −0.86 ± 1.61 mmol·l−1·h−1, P = 0.0198). One subject developed hyponatremia (plasma sodium 128 mmol/l) at exhaustion (2.5 h) in the W trial. A decrease in sodium concentration was correlated with decreased exercise time ( R = 0.674; P = 0.022). A lower rate of urine production correlated with a greater rate of sodium decrease ( R = −0.478; P = 0.0447). Sweat production was not significantly correlated with plasma sodium reduction. The results show that decreased plasma sodium concentration can result from replacement of sweat losses with plain W, when sweat losses are large, and can precipitate the development of hyponatremia, particularly in individuals who have a decreased urine production during exercise. Exercise performance is also reduced with a decrease in plasma sodium concentration. We, therefore, recommend consumption of a sodium-containing beverage to compensate for large sweat losses incurred during exercise.

Plasma Sodium

Salt intake is a major regulator of blood pressure. There is evidence that those who develop high blood pressure have an underlying defect in the ability of the kidney to excrete salt. It has been suggested that this results in a greater tendency to retain sodium and an increased compensatory response that is responsible for the rise in blood pressure. There is also evidence suggesting that small increases in plasma sodium may directly affect blood pressure, independent of the associated expansion in extracellular volume. We reanalyzed 3 types of studies of changing salt intake. (1) An acute and large reduction in salt intake from 350 mmol/d to 10 to 20 mmol/d for 5 days in hypertensives and normotensives was associated with a fall in plasma sodium of approximately 3 mmol/L (P<0.001). (2) Progressive increases in salt intake from 10 to 250 mmol/d by a daily amount of 50 mmol in normotensives caused increases in plasma sodium (P<0.001). (3) Longer-term modest reduction in salt intake in hypertensives was studied in double-blind randomized crossover studies; 1 month of usual salt intake ( approximately 170 mmol/d) compared with reduced salt intake ( approximately 100 mmol/d). There was a decrease in plasma sodium of 0.4+/-0.2 mmol/L (P<0.05), which was weakly but significantly correlated with the fall in systolic blood pressure (r=0.18; P<0.05). These studies demonstrate that an increase or a decrease in salt intake causes changes in plasma sodium. Small changes in plasma sodium alter extracellular volume, which may influence blood pressure. Changes in plasma sodium may also affect blood pressure directly.

Plasma sodium - ignored and underestimated

P-404 Key Words: Salt Intake, Plasma Sodium,

Hyponatremia as a complication of cardiac catheterization: A prospective study

Background: A decrease in plasma sodium (PNa) concentration is common after surgery and attributed to the secretion of antidiuretic hormone in response to such nonosmotic stimuli as pain or nausea. In this setting, acute hyponatremia may lead to seizures, coma, and permanent neurological damage. Sporadic case reports have described severe neurological symptoms caused by hyponatremia occurring within hours after cardiac catheterization. We evaluated the prevalence, contributing clinical circumstances, and course of hyponatremia in patients undergoing cardiac catheterization. Methods: We prospectively studied 309 consecutive patients scheduled for an elective cardiac catheterization. Plasma and urine electrolytes and urine osmolarity were measured at baseline and again 1 to 4 hours and 24 hours after the procedure. Results: PNa level was 139.4 ± 2.3 mEq/L at baseline. At 1 to 4 hours, PNa level decreased to 134.2 ± 3.6 mEq/L (P < 0.0001). Mild (≥5 to 10 mEq/L), moderate (11 to 14 mEq/L), and severe (≥15 mEq/L) reductions in PNa levels occurred in 50%, 5%, and 0.3% of patients, respectively. At the 24-hour point, PNa level increased to 137.3 ± 2.4 mEq/L, but was significantly lower compared with baseline (P < 0.0001). In hyponatremic patients at the 1- to 4- and 24-hour points, mean urine osmolarity values were 428 ± 139 and 420 ± 204 mOsm/kg, respectively; almost every urine sample was inappropriately concentrated. Multivariate logistic regression identified the amount of electrolyte-free water administered to be a predictor for the development of hyponatremia (3.7-fold incremental risk for every 1 L administered to a 70-kg patient). Conclusion: An acute reduction in PNa level commonly occurs shortly after cardiac catheterization. The cause of hyponatremia appears to be related to the administration of hypotonic fluids, together with impaired urinary dilutional capacity. Although symptomatic hyponatremia is rare, the diagnosis should be entertained when neurological symptoms develop in this setting. Am J Kidney Dis 40:940-946. © 2002 by the National Kidney Foundation, Inc.

Renal water handling in rats with decompensated liver cirrhosis.

The present study was performed to investigate the renal handling of water in rats with decompensated liver cirrhosis. Liver cirrhosis was induced by intraperitoneal administration of carbon tetrachloride twice weekly for 16 wk. Control rats were treated with vehicle. The cirrhotic rats developed severe disturbances in water homeostasis: urine production was decreased and hyperosmotic, the rats had significantly decreased plasma sodium concentration and ascites, and the ability to excrete an intravenous water load was significantly impaired. Plasma concentrations of vasopressin and aldosterone were increased. Mean arterial pressure, glomerular filtration rate (GFR), and fractional lithium excretion were decreased. Acute vasopressin type 2-receptor blockade with the selective nonpeptide antagonist OPC-31260 (800 microg. kg(-1). h(-1)) was performed during conditions whereby volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 150 mM glucose. The aquaretic response to OPC-31260 was similar in cirrhotic and control rats. However, the OPC 31260-induced rises in fractional water excretion (delta V/GFR; +24%) and fractional distal water excretion (delta V/C(Li); +46%) were significantly increased in the cirrhotic rats, where V is flow rate and delta is change. This suggests that vasopressin-mediated renal water reabsorption capacity was increased in the cirrhotic rats. Semiquantitative immunoblotting revealed that the expression of the vasopressin-regulated water channel aquaporin-2 was unchanged in membrane fractions of both whole kidney and inner medulla from cirrhotic rats. Together, these results suggest a relative escape from vasopressin on collecting duct water reabsorption in rats with decompensated liver cirrhosis.

Disease and Gill Lesions in Yellow Perch (Perca flavescens) Exposed to Oil Sands Mining-Associated Waters

Adult yellow perch were stocked into experimental ponds designed to test the biological effects of aquatic reclamation alternatives currently being pursued by the oil sands mining industry. Water-quality characteristics of oil sands-influenced water in the experimental ponds included increased salinity and elevated trace organics associated with raw oil sands (bitumen). After 3 and 10 months of exposure to affected waters, perch gross pathologies including severe fin erosion and virally induced tumors were observed in exposed individuals. Gill histopathology revealed large aneurysms accompanied by a proliferation of chloride and epithelial cells in the interlamellar spaces. Gill pathologies were not paralleled by a decrease in plasma sodium, calcium, or chloride. The frequencies of gross pathologies and gill changes were correlated to the concentrations of the oil sands-related compounds. As inorganic and organic compounds associated with oil sands activities are highly intercorrelated, and the observed lesions and changes are not diagnostic of particular toxicants, it was not possible to isolate the causative chemical factor(s) responsible. The incidence of observed lesions and gill pathologies could not be conclusively linked to increased mortality rates observed in the exposed populations. Evidence of recovery in the pathologies was observed between 3 and 10 months of exposure, coincident with a stabilization in population numbers.

Bioaccumulation and Subchronic Physiological Effects of Waterborne Iron Overload on Whitefish Exposed in Humic and Nonhumic Water

One-year-old whitefish, Coregonus lavaretus, were exposed to three types of iron-rich water, two dilutions for each, in a subchronic (30-day) experiment. In natural iron-rich humic water, both the bioaccumulation and physiological effects of iron exposure were negligible. In humic-free water with high amount of additional inorganic iron (nominally 8 mg Fe/L), Fe accumulated in gills, liver, and gut. This accumulation was accompanied by decreased glycogen phosphorylase activities and microsomal EROD activity in the liver as well as decreased plasma sodium and potassium concentrations. The third group of whitefish were exposed by adding inorganic iron (nominally 2 and 8 mg Fe/L) to natural iron-rich humic water. Fish exposed to the higher concentration of waterborne iron exhibited a physiological stress response as indicated by increased blood lactate and plasma cortisol concentrations. Additionally, plasma 17beta-estradiol concentration was increased in fish kept in both water conditions with high amounts of additional iron. The observed dissimilarities in bioaccumulation and in physiological responses were not connected with the measured amounts of total or dissolved iron in water, but to the amount of additional iron in tanks and to the different water conditions with or without organic matter. The dissimilarity of physiological responses, which was also shown by statistical classification through multivariate discriminant analysis, points to the necessity of variable and complementary physiological endpoints in describing the effects of similar kind of exposures.http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p196.html

Brain adaptation to acute hyponatremia in young rats

Brain swelling after acute hyponatremia in prepubescent rats, in contrast to adults, has recently been associated with an increase in brain sodium and a high mortality that could be prevented by preadministration of testosterone. To reexamine the effect of acute hyponatremia in young brain, we measured brain water and solute content in prepubescent rats after induction of hyponatremia over 4 h with water and arginine vasopressin. An 18% decrease in plasma sodium was associated with a 13% increase in brain water and a decrease in brain sodium and glutamate contents. No animals died. To assess the effect of sex hormones on brain adaptation, prepubescent rats were pretreated with estrogen or testosterone before acute hyponatremia. Brain sodium and potassium contents were significantly reduced in comparison to normonatremia in testosterone-pretreated but not estrogen-pretreated animals. However, there was no difference between estrogen-pretreated and testosterone-pretreated groups in mortality or in brain contents of water, electrolytes, or major organic osmolytes. In conclusion, we found that brain adaptation to acute hyponatremia in prepubescent rats is similar to that observed in adults.

Furosemide Decreases Cerebrospinal Fluid Formation During Desflurane Anesthesia in Rabbits

Previous studies suggest that desflurane may increase cerebrospinal fluid (CSF) formation rate (Vf) and volume, particularly during conditions of hypocapnia combined with elevated CSF pressure. The present study was designed to determine whether treatments routinely used in patients during anesthesia for neurological surgery would decrease Vf during desflurane anesthesia in rabbits. Three groups of six rabbits each were examined at four experimental conditions. Condition 1 was the combination of isoflurane, normocapnia, and normal CSF pressure (baseline, all groups). Condition 2 was the combination of isoflurane (group 1) or desflurane (groups 2 and 3), hypocapnia, and elevated CSF pressure (27 and 33 cm H2O). Conditions 3 and 4 were the same as condition 2 with the addition of furosemide, dexamethasone, mannitol, or fentanyl in groups 2 and 3. Vf, resistance to reabsorption of CSF (Ra), and systemic values were determined at each experimental condition, and brain water content was determined at the end of the study. Mean baseline Vf was 9.8 +/- 2.6 microliters.min-1. During the combination of desflurane, hypocapnia, and elevated CSF pressure, furosemide decreased Vf to 3.2 +/- 1.7 microliters.min-1, mannitol increased plasma osmolality and decreased plasma sodium concentration, and fentanyl decreased heart rate and increased plasma potassium concentration. Values for Ra and brain water content did not differ between groups. Of the four treatments examined, only furosemide decreased Vf during the combination of desflurane, hypocapnia, and elevated CSF pressure.

Effects of long-term treatment with enalapril or hydralazine on the renin-angiotensin-aldosterone system and fluid balance in dogs with naturally acquired mitral valve regurgitation

Abstract Objective To study long-term effects of enalapril, an angiotensin-converting enzyme inhibitor, and hydralazine, an arteriodilator, on renin-angiotensin-aldosterone system and fluid balance before and after administration of furosemide. Animals 22 dogs with clinical signs of congestive heart failure (CHF) attributable to mitral regurgitation. Procedure After initial examination, 12 dogs received enalapril and 10 received hydralazine. Dogs were re-examined 3 weeks and 6 months after initial examination. Furosemide was added after the 3-week examination, and at 6 months, dogs had received furosemide for at least 4 months. Results Angiotensin II and aldosterone plasma concentrations were low before treatment, and only aldosterone became significantly decreased after enalapril monotherapy. Concentrations of both hormones and heart rate increased in dogs receiving hydralazine monotherapy, and fluid retention was evident. After long-term treatment with either of the 2 drugs together with furosemide, angiotensin II and aldosterone values increased in both groups. Natriuresis and kaliuresis developed in all dogs, with greatest effect in those receiving enalapril and furosemide. These dogs had decreased plasma sodium concentration, whereas potassium concentration was equally decreased in both groups. After 6 months, the enalapril group, but not the hydralazine group, had increased cardiac size. All dogs had moderate reduction of weight and were azotemic, although changes were more pronounced in those of the hydralazine group. Conclusion The 2 drugs have different effects on the renin-angiotensin-aldosterone system and fluid balance in dogs with CHF. (Am J Vet Res 1996;57:1645–1652)