Sympathetic neural and hemodynamic responses to head-up tilt during isoosmotic and hyperosmotic hypovolemia.

We hypothesized that muscle sympathetic nerve activity (MSNA) during head-up tilt (HUT) would be augmented during exercise-induced (hyperosmotic) dehydration but not isoosmotic dehydration via an oral diuretic. We studied 26 young healthy subjects (7 female, 19 male) divided into three groups: euhydrated (EUH, n = 7), previously exercised in 40°C while maintaining hydration; dehydrated (DEH, n = 10), previously exercised in 40°C during which ~3% of body weight was lost via sweat loss; and diuretic (DIUR, n = 9), a group that did not exercise but lost ~3% of body weight via diuresis (furosemide, 80 mg by mouth). We measured MSNA, heart rate (HR), and blood pressure (BP) during supine rest and 30° and 45° HUT. Plasma volume (PV) decreased similarly in DEH (-8.5 ± 3.3%) and DIUR (-11.4 ± 5.7%) (P > 0.05). Plasma osmolality was similar between DIUR and EUH (288 ± 4 vs. 284 ± 5 mmol/kg, respectively) but was significantly higher in DEH (299 ± 5 mmol/kg) (P < 0.05). Mixed-model ANOVA was used with repeated measures on position (HUT) and between-group analysis on condition. HR and MSNA increased in all subjects during HUT (main effect of position; P < 0.05). There was also a significant main effect of group, such that MSNA and HR were higher in DEH compared with DIUR (P < 0.05). Changes in HR with HUT were larger in both hypovolemic groups compared with EUH (P < 0.05). The differential HUT response "strategies" in each group suggest a greater role for hypovolemia per se in controlling HR responses during dehydration, and a stronger role for osmolality in control of SNA.NEW & NOTEWORTHY Interactions of volume regulation with control of vascular sympathetic nerve activity (SNA) have important implications for blood pressure regulation. Here, we demonstrate that SNA and heart rate (HR) during hyperosmotic hypovolemia (exercise-induced) were augmented during supine and tilt compared with isoosmotic hypovolemia (diuretic), which primarily augmented the HR response. Our data suggest that hypovolemia per se had a larger role in controlling HR responses, whereas osmolality had a stronger role in control of SNA.

Renal support in acute kidney injury.

Acute kidney injury requiring renal replacement therapy (RRT) is associated with an unacceptably high mortality rate. Despite the identification of the modality, timing and intensity of dialysis, membrane biocompatibility, hollow fiber and catheter properties as potential modifying factors, there is little convincing evidence for the superiority of one over the other. However, the available data suggest that the early initiation of RRT may be beneficial. A focused review of clinical trials and meta-analysis of clinical trials of RRT is provided.

Overdose of methyldopa, indapamide and theophylline resulting in prolonged hypotension, marked diuresis and hypokalaemia in an elderly patient.

An 89-year-old man with a history of hypertension, chronic obstructive pulmonary disease, personality disorder and previous attempts of self-poisoning attempted suicide by swallowing two mouthfuls of tablets (methyldopa 250 mg, theophylline SR 200 mg, indapamide 2.5 mg and paracetamol 500 mg). He had prolonged, severe hypotension, necessitating the use of 3000 ml of Gelofusine and almost 2 days of intravenous norepinephrine infusion. He had marked diuresis for 4.5 days, requiring continuous and bolus infusions of intravenous fluids. He had marked renal potassium loss, requiring vigorous potassium replacement therapy. Multiple-dose activated charcoal was used to enhance theophylline elimination. The plasma paracetamol level was below the treatment line. Methyldopa via its metabolite stimulates postsynaptic alpha-adrenergic receptors in cardiovascular control centres in the brain, causing a reduction in peripheral sympathetic tone and a fall in arterial blood pressure and heart rate. In overdose, it causes hypotension, bradycardia and drowsiness. The natriuretic, kaliuretic and vasodilatory effects of indapamide are exaggerated in overdose, resulting in diuresis, hypokalaemia and hypotension. Theophylline markedly increases the level of circulating catecholamines, which stimulate the vascular beta(2)-adrenergic receptors with decreased peripheral vascular resistance. Peripheral vasodilation and hypotension occur in significant theophylline poisoning. Intracellular shift of potassium results in hypokalaemia. The prescribing physicians should recognise elderly patients at a high risk of self-poisoning and avoid using drugs with a high toxicity in overdose (e.g. theophylline and methyldopa). Restricting access to hazardous drugs (in overdose) would be of paramount importance to reduce the number of severe acute poisoning cases and case-fatalities.

Excretion of proteins by rat kidney during various types of diuresis.

Experiments on healthy rats showed that increased diuresis induced by administration of water, polyethylene glycol 400, furosemide, or 1-desamino-arginine-vasotocin is associated with increased protein excretion by the kidneys. The results can be explained by enhanced filtration of plasma proteins in glomeruli during polyuria of various geneses.

Nursing management of patients who are nil by mouth.

This article examines how to manage patients who are nil by mouth (NBM) and maintain optimal nutritional status. Pre-operative fasting and other reasons why patients might be NBM, methods of administering nutritional support and nursing considerations, such as mouth care, urine output, intravenous therapy and skin assessment are also discussed. The article provides an insight into the psychological effects on patients who are NBM and emphasises the importance of patient education.

Massive Post-Obstructive Diuresis.

BACKGROUND The purpose of presenting this case is to demonstrate the degree to which the kidney is capable of selectively excreting a massive load of sodium and water when challenged with both of these, without altering the plasma levels of other ions. CASE REPORT An 8-year-old boy was admitted in severe renal failure. Workup demonstrated a high grade obstruction of a single kidney. Following dialysis, the patient underwent surgery to correct the obstruction and he developed post-obstructive diuresis. Within one week he was receiving 34 liters of essentially 1/2 Na by IV and by mouth and was excreting 70% of his filtered load of water and 50% of his filtered load of sodium. As soon as the administered fluids and Na were cut back, the kidney responded appropriately. CONCLUSIONS While post-obstructive diuresis is a real phenomenon, very frequently it is magnified by forcing diuresis with the administration of too much water. These patients are best treated by administering fluids to equal output for two to three days and then gradually cutting back on fluid intake. If the kidney responds appropriately, then fluids can be given as the patient requests.

Arginine-vasopressin in postpartum panhypopituitarism: urinary excretion and kidney response to osmolar load.

The response to an osmolar load (750 ml 2.5% NaCl solution iv preceded by 500 ml water by mouth) was studied in 20 patients with Sheehan's syndrome and 12 normal women. Sodium and osmolality were determined in plasma and urine and arginine-vasopressin (AVP) was measured by RIA in urine. The test was performed in each patient when untreated (group P), after hydrocortisone replacement alone (group F), and combined hydrocortisone and thyroid hormone replacement (group F+T). After the osmolar loading, maximum urinary osmolality in the patients was lower than in the normal women and remained unaffected by both hydrocortisone alone and hydrocortisone and thyroid hormone. Comparison of the mean hourly urinary volume before and after NaCl infusion demonstrated an increase in group P, a decrease in group C, and no change in groups F and F+T. Although free water clearance became negative in all groups, values in groups P, F, and F+T were constantly above that of group C. None of the patients in groups P and F had a significant rise in urine AVP excretion during or after NaCl infusion. Those in group F+T had a slight AVP response which was less than in normal women. Impaired response of AVP to an osmolar load appears to be a constant feature of Sheehan's syndrome even without overt diabetes insipidus.

Effect of aging and caloric restriction on intestinal permeability.

Intestinal permeability is increased in several disorders such as Crohn's disease or rheumatoid arthritis. Since aging leads to alteration of many biological functions, the effect of aging on intestinal permeability was studied by measuring the intestinal permeability in aging rats gavaged with different size permeability probes--mannitol, polyethylene glycol (PEG) 400, and inulin. In rats fed with control diet, there was a significant increase in intestinal permeability to medium size probes PEG 400 (14.8 +/- 0.4 and 21.0 +/- 1.1% at 3 and 28 months respectively, p less than .01) and mannitol (3.41 +/- 0.4 and 5.3 +/- 0.5% at 3 and 28 months, respectively, p less than .01). Intestinal permeability of the large macromolecule inulin did not change (0.42 +/- 0.03 and 0.38 +/- 0.02% at 3 and 28 months, respectively) with aging. There was no correlation between weight of the rats and their intestinal permeability. Because dietary caloric restriction has been found to prolong the life span, retard deterioration of several biological functions, and affect intestinal absorptive functions, we examined the effect of lifelong calorie restriction on intestinal permeability changes. Lifelong calorie-restricted diet did not affect age-related change in intestinal permeability. We conclude that intestinal permeability of medium size probes increases with aging and that lifelong caloric restriction does not prevent this change. We speculate that age-associated deterioration in intestinal barrier functions could permit increased systemic absorption of lumenal antigens and could perhaps contribute to the genesis of antigen-related age-associated diseases.

Cardiopulmonary effects of 7.2% saline solution compared with gelatin infusion in the early postoperative period after coronary artery bypass grafting.

OBJECTIVE: We report a clinical study on the use of 7.2%, 2400 mOsm/L, hypertonic saline solution compared with gelatin in early postoperative period after coronary artery bypass surgery. METHODS: Two groups (n = 10 each) received 5 ml/kg of either saline solution or gelatin over 1 hour. Cardiac index, central venous pressure, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance indices, arterial oxygen tension, plasma osmolarity, electrolytes, and urinary output were recorded before starting the infusion and subsequently at 10, 30, 60, 90, 120, 240 and 600 minutes. Plasma creatinine, urea, electrolytes, urinary volume, and sodium excretion were measured at 12 and 24 hours. RESULTS: There were no significant demographic or operative difference between the groups. Patients receiving saline solution had a larger diuresis at 12 (p = 0.0008) and 24 hours (p = 0.002), with less positive balance at 12 hours (p = 0.0008). The group receiving saline solution had better cardiorespiratory recovery with shorter extubation time (p = 0.033), and earlier increase in cardiac index with a positive correlation between plasma sodium content and cardiac index. Maximum increase in cardiac index (+31%) occurred at 60 minutes (p = 0.025) associated with 8% increase in plasma sodium content (r = 0.51, p = 0.01), without a concomitant rise in pulmonary capillary wedge pressure. The group receiving gelatin had a linear increase in cardiac index with increasing pulmonary capillary wedge pressure, reaching +16% from baseline by 90 minutes. Compared with the gelatin-treated group, patients receiving saline solution had unchanged systemic vascular resistance index but a significantly lower pulmonary vascular resistance index with a negative correlation to plasma sodium content. There was no difference in levels of urea and creatinine. No side-effect attributable to the use of saline solution was observed.

Application of AN69 hydrogel to islet encapsulation. Evaluation in streptozotocin-induced diabetic rat model.

The polymer AN69 (polyacrylonitrile-sodium methallylsulfonate) is a reference in biocompatibility in the field of hemodialysis. Its use for the encapsulation of living cells has been already described, but this study is the first description of AN69 hydrogel-encapsulated islet isograft in streptozotocin (STZ) diabetic rats. The aim of this work is to evaluate the biocompatibility of the AN69 hydrogel by comparison of the efficacy of free versus encapsulated islets transplanted to balance diabetes. Pancreatic islets are isolated from adult male Lewis rats by a standard collagenase digestion and purified on Ficoll density gradients. The AN69 hollow fiber is obtained by coextrusion of an 8% AN69 collodion. The hollow fiber is filled with islets suspended in agarose at the final concentration of 10,000 islets/ml, closed with surgical clips and implanted. The recipients are rendered diabetic by intravenous injection of STZ. The experimental design includes 4 groups of 8 rats: group 1: control, group 2: diabetic rats intraperitoneally implanted with 6000 free islets, group 3: diabetic rats intraperitoneally implanted with 9000 encapsulated islets, group 4: diabetic control. Weight and fasting glycemia are evaluated twice a week, diuresis once a week. After free islet implantation, rat survival is improved with glycemia below 250 mg/dl during 22 days. Compared to group 2, the status of group 3 is better, with a glycemia below 250 mg/dl during at least 70 days. This tends to demonstrate the biocompatibility of AN69 and is the first step of the validation of the use of AN69 for living cell encapsulation.

Consummatory behavior and urine production after cerebroventricular injection of vasopressin and vasopressin antiserum.

Vasopressin, or vasopressin antiserum, was injected into a lateral cerebral ventricle of conscious rats. These rats were normally hydrated, cellular dehydrated (NaCl loading) or hypovolemic (polyethylene glycol model). Elevation or reduction of vasopressin in cerebrospinal fluid produced no consistent change in consummatory behavior, urine volume or sodium and potassium excretion. These results show vasopressin in cerebrospinal fluid not to be an absolute requirement for maintenance of hydration or for response to acute volume and osmotic stimuli.

Acute kidney toxicity of sodium fluoride in the rat.

Single i.p injection of 0, 0.05, 0.10, 0.25, 0.50 and 1.00 mmol NaF/kg to male rats induced a dose-related increase of urine gamma-glutamyl transferase (GGT) elimination on the first day for all doses higher or equal to 0.25 mmol NaF/kg. Kidney damage began between 2--4 h following the injection and lasted only 12 h for the 0.50 mmol NaF/kg dose. There was an increase of diuresis and of phosphaturia even at lower doses.

Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use.

Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero.

The potential toxicity to neonates of multivitamin preparations used in parenteral nutrition.

This study compares two groups of infants weighing less than 1500 g at birth. In the propylene glycol (PG) group, 30 infants received MVI-Concentrate containing 300 mg of PG daily with their intravenous nutrition (ivn), and vitamin E, 50 mg/week by intramuscular injection. In the mannitol group, 30 infants received MVI-Pediatric (containing 245 mg mannitol), 65% of a vial/day. Serum and urine osmolality, serum PG, blood-urea-nitrogen, creatinine, sodium, and glucose were measured on days 0, 2, 5, 12, 19, 26, 33 and 40 of ivn. Weight, urine output, and fluid intake were measured daily. Vitamin E levels were measured on days 5, 26, and 33 of ivn. There were no significant differences between the groups in birth weight, gestational age, sex, age, or weight at start of ivn. Our results indicated that neither MVI-Concentrate nor MVI-Pediatric was associated with a clinically significant diuresis. MVI-Pediatric, 65% of a vial/day, may produce higher than desirable blood levels of vitamin E, and use of drugs containing PG can produce significant blood levels of PG, in very low birth weight infants.

Assessment of the acute acrylonitrile-induced neurotoxicity in rats.

Acrylonitrile (VCN) is an aliphatic nitrile which is used extensively in manufacturing of synthetic fibers, plastics, and rubber. Although the neurotoxicity of VCN is recognized, no thorough characterization of this effect has been reported. Current studies were designed to quantitatively characterize the acute phase of VCN-induced cholinomimetic neurotoxicity, and to determine the effects of dose, route of administration, and atropine on such toxicity. Administration of a single gavage or subcutaneous doses of 20, 40, or 80 mg VCN/kg to male Sprague-Dawley rats causes two distinctive phases of acute neurotoxic effects. Signs observed in the early phase had a rapid onset, and were cholinomimetic in nature. They included salivation, lacrimation, chromodacryorrhea, polyuria, miosis, vasodilatation in face, ears and extremities, increased gastric secretion, and diarrhea. A late phase developed hours after VCN dosing, and the toxic signs included depression, convulsions, and respiratory failure followed by death at high doses. These results revealed that the cholinomimetic toxicity induced by VCN was dose related regardless of the route of administration. In another study, rats were pretreated with atropine (1 mg/kg, IP) prior to VCN (40 mg/kg) in order to investigate the role of the cholinergic system. Atropine protected rats against VCN-induced cholinomimetic neurotoxicity, suggesting possible involvement of the cholinergic system. Finally, this work provides essential basic information for studying the biochemical, pharmacological, and neurological basis of VCN-induced neurotoxicity in the rat.

Stent of shape-memory alloy for urethral obstruction caused by benign prostatic hyperplasia.

Dilation and positioning a stent in the prostatic urethra have become important alternatives for the management of benign prostatic hyperplasia (BPH), but both have significant drawbacks, namely the need to repeat the treatment in the former case and the conflict between the introducing means and the generation of sufficient expansile force in the latter case. A spiral of a Chinese titanium-nickel alloy with shape memory was implanted in 25 patients with BPH using a self-made coaxial sheath. With a follow-up of 3 to 20 months, the success rate is 92%. There has been no encrustation or migration of the spirals. We deem the spiral of this shape-memory alloy to be a good alternative in patients with BPH who are unfit for surgery.

Relationship between plasma beta 2-microglobulin and residual diuresis in continuous ambulatory peritoneal dialysis and hemodialysis patients.

To evaluate whether the continuous ambulatory peritoneal dialysis (CAPD) technique is able per se to obtain lower beta 2-microglobulin (beta 2M) plasma levels than hemodialysis (HD) or whether other factors, such as residual diuresis, can make a significant contribution, we compared 69 CAPD and 38 cuprophan HD patients, matched for age and dialysis duration. Residual diuresis was 680.3 +/- 531.8 mL/day in CAPD and 285.5 +/- 381.8 mL/day in HD (p < 0.001) subjects. Daily diuresis was > 300 mL/day in 63.8% of CAPD and in 31.6% of HD patients. The beta 2M plasma levels were 26.3 +/- 9.9 mg/L and 34.9 +/- 13.3 mg/L (p < 0.001) in CAPD and HD, respectively. In both groups the difference was significant when we compared the patients with diuresis below versus above 300 mL/day (p < 0.001). Instead, the differences were not significant upon comparing the CAPD and HD patients with the same amount of daily diuresis. The comparison between beta 2M plasma levels and residual diuresis showed a significant inverse correlation in both groups (p < 0.001). We conclude that the dialysis technique itself does not affect beta 2M plasma levels. The diuresis volume may be a very important factor in lowering beta 2M levels in both CAPD and HD patients. CAPD's capacity to maintain a higher diuresis for longer than HD may account for the lower beta 2M plasma levels in CAPD patients.

A fluorocarbon-coated diuresis cage for rodents.

A simple and inexpensive rat diuresis cage is described. It may be constructed from thin aluminium sheeting in combination with a standard laboratory holding cage. Application of a low resistance PTFE coating reduces urine losses to a level better than a leading commercial design. Some physiological strain comparison data obtained using the cage are given.

Effects of a multi-hour immersion with intermittent exercise on urinary excretion and tilt table tolerance in athletes and nonathletes.

The circulatory and diuretic responses of athletes and non-athletes to 6-h water i-mersion with intermittent swimming exercise (series I) as well as to 8-h inactive immersions (series II) were studied. With simultaneous intermittent exercise, the normally arising diuresis during a water bath was strongly suppressed in athletes and even abolished in nonathletes. In subsequent tilt table tests, 3 of 11 (27.3%) athletes of series I and 3 of 4 (75%) of series II collapsed, whereas all nonathletes tolerated the vertical position without any subjective complaints. By use of the so-called "orthostatic index" (4) the later group, however, was also shown to yield a substantially better orthostatic stability in series I than in series II. The protective effect of intermittent physical activity for simulation of the weightless state can possibly be explained by assuming a less-reduced plasma volume via a diminished urinary excretion.

Reduced tolerance of simulated altitude (4200 m) in young men with borderline hypertension.

BACKGROUND: Primary hypertensives who are acutely exposed to hypoxic hypoxia show an enhanced reactivity of arterial chemoreceptors as well as an exaggerated response of the sympathetic nervous system. Since these phenomena could influence their ability to tolerate sustained hypoxic hypoxia, this study was performed to determine whether persons predisposed to hypertension have a normal tolerance of simulated high altitude. METHODS: Subjects were 18 young men with a family history of hypertension (sons of hypertensives, SOHT) whose BP values were in the upper normal or borderline hypertensive range. Controls were 15 young men without parental hypertension (sons of normotensives, SONT) who had normal BP values. Each subject underwent both a control and an altitude experiment. The latter consisted of an 8-h exposure to hypobaric hypoxia (equivalent to 4200 m) while resting supine in an altitude chamber. Fluids were administered by mouth and by intravenous line to produce sustained diuresis. Variables measured included heart rate, BP, respiratory rate, O2 saturation, urine flow rate, and sodium excretion. RESULTS: All subjects tolerated the control experiment and all SONT also completed altitude exposure. However, 8 of 18 SOHT developed antidiuresis and had to leave the chamber early due to symptoms of mild acute mountain sickness. Compared with SONT, SOHT exhibited more stable cardiorespiratory parameters at altitude. CONCLUSIONS: The data support the hypothesis that borderline hypertensives have stronger cardiorespiratory responses to altitude than controls, a response that is compatible with higher excitability of their arterial chemoreceptors. However, their altitude tolerance is reduced even at rest, probably because of the renal effects of an exaggerated response in the sympathetic nervous system.