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PubMed1997

Effect of kappa opioid agonist RU 51599 on osmotic and non-osmotic stimulated arginine vasopressin release and gene regulation in small cell lung carcinoma cells.

Arginine vasopressin (AVP) is synthesized in the hypothalamus, stored in the posterior pituitary, and osmotic and non-osmotic stimuli release AVP into the circulation for antidiuretic and vascular actions on target tissue. The kappa-opioid agonist, RU 51599, exhibits a potent diuretic activity in both experimental animals and humans. This diuretic activity is characterized by a water diuresis without an associated increase in electrolyte excretion. Studies with cultured rat hypothalamo-neurohypophysial system explant showed that AVP mRNA level changed in parallel to the RU 51599-induced changes in AVP secretory rate. There are, however, no hypothalamic neuronal cell lines to study AVP gene regulation system, and it is not known whether RU 51599, regulates AVP secretion and biosynthesis under osmotic and non-osmotic stimulatory conditions of AVP release. The effect of RU 51599 on AVP release, AVP mRNA, and AVP gene promoter activity in osmotic and non-osmotic conditions was therefore studied using cultured small cell lung carcinoma (SCLC) cell lines. RU 51599 significantly inhibited AVP release by osmotic stimulation (330 mOsm) and non-osmotic stimulators, angiotensin II (AII) and endothelin 3 (ET3). However, RU 51599 did not show any effect on the AVP mRNA and AVP gene promoter activity stimulated by high osmolality and ET3. These results indicate, therefore, that RU 51599 suppresses AVP secretion by inhibition at the step of AVP release during osmotic and non-osmotic stimulation but does not affect the AVP gene transcription level in the SCLC cells.

Angiotensin II↗
PubMed1997

Using information management to implement a clinical resource management program.

BACKGROUND: This article provides a consultant's account of a 250-bed community hospital's experience in implementing the Clinical Resource Management (CRM) program, a four-stage process of using information to identify opportunities for improvement, developing an effective resource management team, implementing process improvement activities, and measuring the impact on outcomes of care. CASE STUDY EXAMPLE--CONGESTIVE HEART FAILURE: The chair of the departments of internal medicine and family practice selected congestive heart failure for in-depth study. A task force focused on treatment and patient disposition in the emergency room (ER), where most of the nonelective admissions originated. A set of standardized ER orders was developed that emphasized rapid and effective diuresis through the initiation of a progressive diuretic dosing schedule directly linked to patient response. LESSONS AND REFLECTIONS: Factors critical to the success of the CRM program included allocating adequate time to promote and sell the value and importance of the program, as well as securing the support of both information systems and physicians. The main barriers to success involved limitations in the information system infrastructure and delays attributable to committee review. Short-term results from the CRM program were encouraging, with average lengths of stay reduced by 0.5 days and average costs of care reduced by 12% for the ten diagnoses studied with no adverse results. Nonstudy diagnoses showed no notable improvement. CONCLUSIONS: Recognizing the growing importance of information management not only for clinical decision support but for accommodating all the necessary internal and external reporting requirements will require a significant commitment and investment in technology and personnel resources.

Arthroplasty, Replacement, Hip↗
PubMed2001

The choice of timing for diuresis renography: the F + 0 method.

OBJECTIVE: To investigate a method of diuresis renography where the radiopharmaceutical and frusemide (diuretic) are given simultaneously, in contrast to conventional renography which involves an intravenous injection with frusemide 20 min after administering the radiopharmaceutical (F + 20) or 15 min before (F - 15), with particular interest in the effect of this change on assessing split renal function and interpreting upper tract drainage dynamics. PATIENTS AND METHODS: In a prospective study, 29 patients (18 women and 11 men, mean age 47 years, range 21--86) were assessed. Each patient had two renograms taken over a 48-h period, either by the F + 20 or F - 15, and the F + 0 method: Data for split renal function and drainage curves were obtained in the usual way. Two independent assessments of the drainage curves were obtained and the results compared. RESULTS: The split function assessments were identical (< 5% variation) in all but two patients; 26 of 29 (90%) gave identical conclusions about the drainage curves. The three patients with discrepancies between the studies had either hugely dilated upper tracts or otherwise had multiple complicating factors, e.g. impaired renal function, neuropathic bladder. CONCLUSIONS: F + 0 renography has been used in paediatric urological practice before, but there are no comparative studies and no data on its use in adults. This prospective study confirmed that in investigating dilated upper tracts, the F + 0 technique gives similar results to the conventional techniques. The F + 0 method has the potential to reduce the time required to undertake standard F + 20 renography but it may not be useful in evaluating the grossly dilated upper tract, where the F-15 technique has the best record in terms of reducing equivocal results.

Adult↗
PubMed1987

[Improvement in the informativeness of diuretic kidney function scintigraphy by calculation of a washout index].

Diuresis renography after administration of 123I-(131I-)Hippuran of 248 patients (492 kidneys) were compared retrospectively with clinical findings, history, i.v. urography, and ultrasound examinations. A new wash-out-index was calculated. In cases with obstructive dilatation of the collecting system this index was smaller than 0.9. If it was 0.9 to 1.2 additional diagnostic procedures seem necessary. An index more then 1.4 excludes obstruction. The shape of the renogram curve after furosemide is important for the diagnosis too. A concave shape was found in non-obstructive dilatation, a convex shape in obstructive dilatation of the renal pelvis. The wash-out-index is a reliable parameter if cases with reflux, lower ureteral obstruction and shrunken kidneys are excluded.

Humans↗
PubMed2002

Dexamethazone-induced acute tumor lysis syndrome in a T-cell malignant lymphoma.

We report a case of steroid-induced acute tumor lysis syndrome and review the literature. A 60-year-old woman was started on steroid therapy for dyspnea due to bilateral pleural effusion and a large mass involving the anterior mediastinum. The final diagnosis was precursor T-lymphoblastic lymphoma-leukemia. Following steroid therapy, the patient developed acute renal failure and laboratory evidence of metabolic changes induced by massive cytolysis. She received vigorous hydration, diuretic and allopurinol therapy, and haemodialysis. Her diuresis, renal function and laboratory data returned to normal within 2 weeks. A review of the medical literature on T-cell lymphoma revealed only one similar case of steroid-induced acute tumor lysis syndrome, a life-threatening metabolic emergency. This risk should be kept into account in the management of patients with lymphoproliferative disorders.

Acute Disease↗
PubMed1993

Effects of AE0047 on renal haemodynamics and function in anaesthetized dogs.

1. The effects of AE0047, a newly developed calcium channel blocker, on renal haemodynamics and function were investigated and compared with those of nicardipine in anaesthetized dogs. 2. Intravenous injection of AE0047 (10 and 30 micrograms/kg) caused a dose-related fall in blood pressure (BP). The AE0047-induced fall in BP was of slow onset and long lasting. AE0047 at 10 micrograms/kg elicited a slight increase in renal blood flow (RBF) and urine formation. 3. When AE0047 was infused intrarenally at non-hypotensive doses (25 and 50 ng/kg per min), there was no significant increase in RBF. However, the glomerular filtration rate increased significantly after drug infusion. Intrarenal arterial (i.r.a.) infusion of AE0047 led to dose-related increases in urine flow (UF), urinary excretion of electrolytes (Na+, K+ and Cl-) and fractional excretion of electrolytes. The AE0047-induced increase in urine formation was of very slow onset and progressed even after the cessation of the AE0047 infusion. 4. The intrarenal arterial infusion of nicardipine at same doses as AE0047 produced significant increases in urine formation, but these effects were immediately restored to the control values after cessation of the nicardipine infusion. 5. It was shown that AE0047 has a long-lasting diuretic effect and that AE0047-induced diuresis may be due to inhibitory effects on sodium and water reabsorption in the renal tubules.

Anesthesia↗
PubMed1985

Signals from the oropharynx may contribute to the diuresis which occurs in man to drinking isotonic fluids.

The drinking of a variety of isotonic salt solutions provoked a short load-dependent diuretic response in man, similar in latency to that of a water diuresis and reaching its maximum 40-60 min from the start of drinking. Subjects differed in the threshold load at which the response became evident, and also in the magnitude of their responses. Changes in free water clearance matched the increases in urinary minute volume, with no significant change in either urinary sodium or potassium excretion. Changes in urinary pH and in ammonium excretion were similar to those described for a water diuresis. Drinking an isotonic solution of mannitol provoked a diuresis similar to that of the salt solutions. All subjects had diarrhoea after drinking the mannitol. Signals arising from the oropharynx might be partly responsible for eliciting the diuresis. The significantly smaller urinary responses to infusions of isotonic salt solutions directly into the stomach support this view. The absence of a significant response to 'sham drinking' appears inconsistent with this, but oropharyngeal signals may only have a priming role in man and interact with other signals to give the full response.

Adult↗
PubMed1988

Atrial natriuretic factor in the pediatric intensive care unit.

ANF is a newly discovered peptide hormone that has significant implications for critical care physicians. This hormone, released from the heart, is especially responsive to fluid challenges as well as to many of the drugs commonly used in the ICU, including pressor and anesthetic agents. It has potent arterial vasodilating effects in pharmacologic doses and may be an important natural vasodilating agent, especially in the renal vascular bed. In patients on dopamine, it may potentiate the renal vasodilating effect and may provide an effective therapy for developing acute renal failure. Children with congenital heart disease and patients with CHF have elevated levels that clearly alter the aldosterone-angiotensin II system and may help us to understand and treat these conditions more effectively. Additionally, ANF may be a marker for adequacy of treatment in these disease states. The potential uses for ANF include diuresis in patients with fluid overload and diuretic resistance, treatment of CHF, and as a short-acting vasodilator. In the ICU, many therapies affect cardiac pressures and volume regulation. Positive-pressure ventilation may decrease the release of ANF by decreasing venous return and thus contribute to water retention. Drugs used in the ICU may directly affect ANF levels and markedly affect the homeostasis of fluid and electrolyte balance. This hormone system interacts intimately with renin, angiotensin II, and aldosterone. These interactions may play a significant role in the development of essential hypertension. Although not addressed in this article, the treatment and understanding of essential hypertension may be significantly advanced by understanding these relationships. It is clear that ANF acts as a hormone with complex interactions between the heart, volume status, electrolyte balance, renin-angiotensin II-aldosterone, vasopressin, and vascular tone. Although currently no definitive picture exists for these complex interactions, this is an exciting new hormone with significant implications for patient management in the ICU. As research continues, the picture will become clearer and our understanding of this new hormone more precise.

Animals↗
PubMed1988

General pharmacology of ramipril.

General pharmacological properties of (+)-(1S,3S,5S)-2-[(S)-N-[(S)-1-ethoxycarbonyl-3-phenyl-propyl] alanyl]-2-azabicyclo[3.3.0]octane-3-carboxylic acid (ramipril, Hoe 498), a new prodrug non-sulfhydryl angiotensin converting enzyme inhibitor and its active diacid metabolite, ramiprilat, were examined. Both ramipril and ramiprilat were without effect on basal central and autonomic nervous systems in rats and mice. Ramipril given intravenously to anaesthetized normotensive dogs produced a slight fall in blood pressure but did not significantly alter other cardio-hemodynamic functions. Also, ramiprilat was without effect on isolated atria and airway resistance of guinea pigs. Oral administration of ramipril to dogs increased renal blood flow but did not significantly affect other renal parameters, for example, glomerular filtration rate and electrolyte excretion. Ramipril produced a competitive inhibition of late proximal tubular secretion which points to in part renal secretory excretion of ramipril and/or its metabolites. Compared to urea-induced diuresis in rats, ramipril was without direct diuretic activity. Ramipril exerted little, if any, influence on gastric bile and pancreatic secretion or intestinal transit in rats, as well as on concentration of glucose and lipoproteins, blood coagulation, platelet aggregation and vascular permeability in rats, rabbits or dogs. The carrageenin-induced rat paw edema was enlarged by ramipril, but there was no such effect on serotonin-, dextran- or ovalbumin-induced edemas which in contrast to carrageenin do not involve bradykinin. Thus, undesired cutaneous reactions might result from locally released bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Acute aquaresis by the nonpeptide arginine vasopressin (AVP) antagonist OPC-31260 improves hyponatremia in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

The present study was undertaken to determine whether the non-peptide V2 arginine vasopressin (AVP) antagonist 5-dimethylamino- 1[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepi ne hydrochloride (OPC-31260) produces water diuresis and improves hyponatremia in patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Eleven patients (9 males and 2 females, 64 +/- 3.5 yr) with SIADH were included in the present protocol, which was comprised of 3 successive days. Day 1 was a control day, and on days 2 and 3 OPC-31260 was administered intravenously. Five blood and urine collections were made at 1-2 h intervals during the 6 h observation period each day. A single administration of 0.25 and 0.5 mg/kg OPC-31260 increased the 4 h cumulative urine volume and decreased urinary osmolality to below 225 mOsm/kg H2O. Such a diuretic effect was independent of an increase in urinary solute excretions. This aquaresis by 0.5 mg/kg OPC-31260 caused a significant increase in serum sodium level by approximately 3 mEq/L. The antagonistic effect of OPC-31260 lasted for 4 h when it was given intravenously. These results indicate that OPC-31260 is an effective therapeutic agent for hyponatremia in patients with SIADH.

Aged↗
PubMed1985

Pharmacology and pharmacokinetics of drugs used to treat cardiac disease in horses.

The rational therapy of cardiovascular disease in horses requires a thorough knowledge of the pharmacology and pharmacokinetics of several specific drugs (digitalis, digoxin). Calcium solutions, dopamine, and dobutamine are frequently used to treat congestive heart failure in horses. Quinidine, procainamide, lidocaine, and propranolol are used to treat a variety of supraventricular and ventricular arrhythmias. Furosemide, a highly potent loop diuretic, is used to eliminate edema and promote diuresis. A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and practical considerations must be attained before these drugs can be used effectively.

Administration, Oral↗
PubMed1995

Circulating concentrations and physiologic role of atrial natriuretic peptide during endotoxic shock in the rat.

OBJECTIVES: To determine if there are changes in circulating concentrations of endogenous atrial natriuretic peptide and the physiologic role of this peptide in endotoxic shock. DESIGN: A prospective, randomized, controlled animal trial. SETTING: University research laboratory. SUBJECTS: Anesthetized male Wistar rats, weighing 250 to 350 g. INTERVENTIONS: Six rats received 1.5 mg/kg body weight of lipopolysaccharide alone. Five rats received 1.5 mg/kg of lipopolysaccharide and 200 microL/100 g body weight of rabbit anti-atrial natriuretic peptide serum. Another five rats received 1.5 mg/kg of lipopolysaccharide and normal rabbit serum in the same volume as the antiserum. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of atrial natriuretic peptide, arginine vasopressin, and aldosterone were measured, and changes in hemodynamic parameters and renal function were monitored in rats with endotoxic shock after catheterization of the right jugular vein. Urine volume, urine sodium excretion, urinary potassium excretion, and urine 3', 5'-cyclic guanosine monophosphate (cGMP) excretion were measured at 12-hr intervals. The plasma atrial natriuretic peptide concentration was slightly but significantly lower 30 mins after the lipopolysaccharide injection (114.8 +/- 9.0 pg/mL at 0 hr, 75.6 +/- 6.2 pg/mL at 30 mins, p < .01) and then began to increase, peaking at 6 hrs (752.8 +/- 104.5 pg/mL, p < .01 vs. 0 time) and remaining at higher concentrations than before the preinjection value, up to 24 hrs. In contrast, acute spike-like increases of arginine vasopressin and aldosterone concentrations were observed 30 mins after the lipopolysaccharide injection, preceding the increase of the plasma atrial natriuretic peptide concentration. Measurements of urine volume and urine sodium excretion showed oliguria during the initial 12 hrs after the lipopolysaccharide injection, followed by diuresis and natriuresis during the subsequent 12 hrs. In addition, injection with anti-atrial natriuretic peptide serum in the diuretic phase 12 hrs after the lipopolysaccharide injection significantly inhibited the diuresis, natriuresis, and urine cGMP excretion in this model. Furthermore, the plasma aldosterone concentration 24 hrs after the lipopolysaccharide injection was significantly increased by the administration of the antisera. CONCLUSIONS: These findings suggest that endogenous atrial natriuretic peptide increases in the acute phase of endotoxic shock and plays an important role in water and electrolyte balance by regulating diuresis.

Aldosterone↗
PubMed1987

[Peritoneal dialysis in the treatment of the low cardiac output after extracorporeal circulation].

Low cardiac output after cardiopulmonary bypass is not uncommon. This per- and postoperative cardiac depression is accompanied by an impairment of renal function, which recovers with the improvement of the low cardiac output. These two correlated failures may become resistant to cardiotonic and diuretic drugs. Indeed the fluid balance is strongly disturbed, although venous pressure is only moderately increased. The only possible treatment could be water withdrawal. Nine patients are reported, all suffering from cardiac and renal failure after cardiopulmonary bypass. They were successfully treated with the method of continuous ambulatory peritoneal dialysis. This method allowed us to stop all intravenous cardiac drugs within 36 h, whilst diuresis reappeared together with a better efficacy of diuretic drugs. This beneficial haemodynamic effect of water withdrawal is discussed. This phenomenon may be related to an influence of right ventricular filling on the left ventricle. Low cardiac output may occur as a result of septal displacement, especially if there is concomitant myocardial suffering. Withdrawing a small volume of water may have modified the septal displacement, and improved cardiac output. Continuous ambulatory peritoneal dialysis was simple and well tolerated; it seemed to have contributed to the haemodynamic recovery of all the nine patients.

Aged↗
PubMed1989

Loop diuretics combined with an ACE inhibitor for treatment of hypertension: a study with furosemide, piretanide, and ramipril in spontaneously hypertensive rats.

Both angiotensin converting enzyme (ACE) inhibition and sodium-diuresis lower blood pressure in spontaneously hypertensive rats (SHR). The purpose of the present study was to examine whether long-term therapy with ramipril (RA, and ACE inhibitor) would lower blood pressure more effectively and without adverse reactions in combination with the loop diuretics piretanide (PI) or furosemide (FU). Groups of 15 SHR each were treated once daily for 3 weeks by gavage with 1 and 10 mg/kg RA, 2 and 4 mg/kg PI, and 8 and 16 mg/kg FU alone and with 1 mg/kg RA in combination with each of these diuretics at both the high and low doses. Sustained and marked ACE inhibition with 10 mg/kg RA normalized BP, but this was accompanied with slightly impaired kidney function as assessed by increases in both urea and creatinine. Low-dose diuretic therapy, producing little diuresis, or treatment with 1 mg/kg RA, producing less sustained ACE inhibition were less effective on blood pressure and scarcely altered serum solute levels, except 4 mg/kg PI, which produced slight reductions in Na+, K+, Mg2+, and PO4(3-). Combined treatment with the 1 mg/kg RA with either diuretic given at low or high dose was well tolerated at much improved reduction in blood pressure compared to their effects individually and without changes in serum solute concentrations and without hemoconcentration. Thus, combined treatment with low doses of loop diuretics and ACE inhibitors that permit partial recovery of serum ACE activity during the 24 h after dosing synergistically lowers blood pressure without adverse reactions associated with larger doses of either therapy alone.

Aldosterone↗