Intravenous Infusion Of Furosemide Research Articles

Case Report of Polycystic Kidney Disease in a Persian Cat in IPB University Veterinary Teaching Hospital

A 7-year-old male Persian cat was referred to IPB University Veterinary Teaching Hospital with clinical signs of lethargy, weight loss, and loss of appetite and was diagnosed with nephrolithiasis before being referred to IPB University Veterinary Teaching Hospital. Physical examination revealed tachycardia, tachypnoea, pale mucous membrane, 5–6% dehydration rate, cachexia, and palpated masses on the left and right side of the abdominal region. The abdominal cavity was seen as more radiopaque, which resulted in some organs being invisible in the radiographic view. Abdominal ultrasonography showed abnormalities in the liver, gall bladder, and kidneys. The patient was diagnosed with polycystic kidney disease (PKD) with the prognosis of infausta, as the patient was already in a sternal recumbency and could not stand by himself. During hospitalization, the patient was force-fed with a commercial renal diet, and the medical treatments given were intravenous ceftriaxone, vitamins, furosemide, Azodyl®, and intravenous infusion. The patient regained standing ability and survived until the seventh day of hospitalization. However, the owner persisted in bringing the patient home on the seventh day of hospitalization, and the patient died the next day after being brought home.

Retracted: The Application of Dopamine Combined with Intravenous Furosemide Infusion Therapy Has an Apparent Clinical Effect in Treating Patients with Heart Failure.

[This retracts the article DOI: 10.1155/2022/1055160.].

Advanced heart failure: parenteral diuretics for breathlessness and peripheral oedema – systematic review

BackgroundAdvanced heart failure patients suffer with breathlessness and peripheral oedema, which are frequently treated with parenteral diuretics despite limited evidence.AimTo analyse the effectiveness of parenteral diuretics on breathlessness and peripheral...

The Application of Dopamine Combined with Intravenous Furosemide Infusion Therapy Has an Apparent Clinical Effect in Treating Patients with Heart Failure.

Objective To observe the efficacy and safety of dopamine plus furosemide in treating patients with heart failure. Methods This research included 150 patients with heart failure who were diagnosed and treated at our hospital between March 2018 and November 2020. The patients were randomly assigned to a study group or a reference group according to the data of admission (the cut-off date was June 2019). Patients in the reference group were given furosemide, whereas those in the study group were given dopamine plus furosemide intravenous pumping. Outcome measures included clinical effectiveness, heart function changes, and adverse responses. Results Dopamine plus furosemide resulted in higher treatment efficiency (96.00%) versus furosemide (74.67%) study group (P < 0.05). Before therapy, there was no significant change in the scores of cardiac function indices between the two groups (P > 0.05). The cardiac function of the two groups of patients was improved after treatment, and the left ventricular ejection fraction (LVEF) of the study group (44.85 ± 4.12) was higher than that of the reference group (38.45 ± 4.36), and the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVESD), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) (43.17 ± 3.98, 51.32 ± 4.25, 3045.56 ± 365.48) were lower than the reference group (47.56 ± 4.65, 56.28 ± 4.85, 4856.48 ± 395.46) (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). Conclusion Dopamine plus intravenous furosemide infusion treatment has an obvious therapeutic benefit in treating patients with heart failure and dramatically enhances cardiac function without noteworthy adverse responses. It demonstrated great potential for clinical promotion.

The effect of active diuretic therapy on the sodium balance in patients with acute decompensation of chronic heart failure

Background. Active dehydration of patients with acute decompensation of chronic heart failure (АDCHF) was often accompanied by the development of hyponatremia. This increased the time of hospitalization and worsened the prognosis. The complication was associated with the side effects of furosemide.&#x0D; Aim. To compare the effect of dehydration and the state of sodium balance after using different methods of parenteral administration of furosemide at an early stage of treatment of АDCHF.&#x0D; Materials and methods. Patients with АDCHF (n=125) were divided into two groups. Group 1 received furosemide as bolus injections, group 2 as an extended intravenous infusion. The process of dehydration was controlled by the amount of urine and body weight loss per day. The effect was considered satisfactory if the body weight decreased by 1.02.0 kg per day. The plasma sodium level was studied on 1, 5, 10 days.&#x0D; Results. In group 2, the satisfactory effect of dehydration was observed 1.7 times more often than in group 1 (p0.05). In group 2 patients on the 5th day of therapy, the number of cases of hyponatremia was 2.3 times less (p0.05). Hyponatremia developed little in patients with a satisfactory effect of dehydration. On the 10th day, the number of cases of hyponatremia in the groups did not significantly differ.&#x0D; Conclusion. Prolonged intravenous infusion of furosemide allowed more control of the dehydration process and the plasma sodium level at an early stage of therapy in patients with АDCHF.

A life-threatening case of pseudo-aldosteronism secondary to excessive liquorice ingestion

BackgroundLiquorice is found in many food products, soft drinks, and herbal medicines. Liquorice ingestion is an uncommon cause of apparent mineralocorticoid excess or pseudo-aldosteronism. The mechanism involves the inhibition of 11-beta-hydroxysteroid dehydrogenase type-2 by the active ingredient called glycyrrhizin. This leads to the uninhibited activation of mineralocorticoid receptors by cortisol. Confectionary products that contain liquorice are readily available in many countries around the world.Case presentationWe report a case of severe refractory hypokalaemia with hypertensive crisis and acute pulmonary oedema due to excessive liquorice consumption. A 79-year-old female presented to the emergency department following a road traffic accident. She described feeling weak and dizzy while driving before the collision. She attended her general practitioner (GP) several weeks earlier for fatigue and was being managed for hypokalaemia on oral potassium supplements. Investigations revealed hypertension (BP 180/69 mmHg), severe hypokalaemia (K 2.2 mmol/l), normal renal function, normal serum magnesium with metabolic alkalosis. Spot urinary potassium was 22 mmol/l. The patient denied taking medications including over-the-counter or herbal medication that can cause hypokalaemia. Hypokalaemia persisted despite aggressive intravenous (i.v.) and oral potassium replacement. She later developed a hypertensive crisis (BP 239/114 mmHg) with pulmonary oedema. She required admission to the intensive care unit and was managed with intravenous furosemide infusion and isosorbide dinitrate infusion. On further discussion, our patient admitted to struggling with nicotine cravings since quitting smoking two months earlier. She began eating an excessive amount of liquorice sweets to manage her cravings. Suppression of plasma renin and aldosterone supported the diagnosis of apparent mineralocorticoid excess secondary to excessive liquorice consumption. Her symptoms and hypokalaemia resolved after stopping liquorice intake.ConclusionsThis case highlights the life-threatening and refractory nature of hypokalaemia secondary to excessive liquorice consumption. This case also emphasizes the importance of comprehensive history taking including dietary habits. Increased awareness among the public is required regarding the potential health hazards of excessive liquorice consumption.

Continuous versus intermittent use of furosemide in patients with heart failure and moderate chronic renal dysfunction.

AimsThere is paucity of clinical data comparing continuous infusion (CI) with bolus injection (BI) of intravenous loop diuretics in patients with acute decompensated heart failure (ADHF) and chronic renal dysfunction. This study aimed to compare the efficacy and safety of CI versus BI intravenous furosemide administration in patients with ADHF and moderate chronic renal insufficiency.Methods and resultsAcute decompensated heart failure and moderate chronic renal insufficiency [with estimated glomerular filtration rate (eGFR) 15.0–44.9 mL/min/1.73 m2] were randomized to start intravenous furosemide by BI or by a 6 h CI. End points included freedom from congestion at 72 h, the degree of dyspnoea assessed using the 0–10 Borg's category ratio scale, net daily urine output, weight loss during the study, length of hospital stay, total urinary sodium excretion, and development of acute kidney injury or electrolyte disturbance. After 72 h of treatment, the rate of the primary endpoint of freedom from congestion in the CI group was significantly higher than that in the BI group (69.05% vs. 43.59%, P = 0.02). The modified Borg scale indicated patients in the CI group had lower dyspnoea score than those in the BI group at 48 h (4.29 ± 1.23 vs. 5.97 ± 1.56; P = 0.02) and 72 h (1.15 ± 0.35 vs. 2.66 ± 0.83; P = 0.003). There were other significant differences favouring the CI group with regard to net urine output at 72 h (5145.98 ± 621.37 mL vs. 3755.95 ± 456.93 mL; P = 0.007), the mean body weight loss (4.72 ± 1.01 kg vs. 3.53 ± 0.73 kg; P = 0.02) and the total urinary sodium excretion (385.05 ± 38.15 vs. 320.33 ± 37.67; P = 0.02). The length of hospitalization in the CI group was significantly shorter than that in the BI group (10.36 ± 4.20 days vs. 15.68 ± 6.15 days; P = 0.02). No significant differences were observed between groups in the frequency of acute kidney injury, tinnitus, electrolyte disturbance or mortality.ConclusionsContinuous intravenous infusion of furosemide resulted in significantly greater diuresis than bolus administration of an equal dose in patients with moderate chronic renal insufficiency and ADHF, while no differences emerged in terms of side effects or mortality.

Crossing the chasm: caution for use of angiotensin receptor-neprilysin inhibition in patients with cardiogenic shock- a case report.

BackgroundVasoplegia has been reported in patients receiving angiotensin receptor-neprilysin inhibitors (ARNI) with heart failure with reduced ejection fraction (HFrEF). We present a case of vasoplegic shock after initiation of ARNI in a hospitalized 65-year-old man recovering from cardiogenic shock (CS) and acute kidney injury (AKI).Case summaryA 65-year-old man with HFrEF presented to a community hospital with CS with evidence of poor perfusion with a lactate of 5.6 mmol/L and creatinine (Cr) 125 µmol/L. He was treated with intravenous furosemide infusion. Subsequently, his lactate normalized but he developed an AKI with a Cr of 176 µmol/L. He was then started on ARNI and beta blockers. Over the next 24 h, he developed a vasoplegic shock necessitating multiple vasopressors and a transfer to a tertiary academic centre. With supportive therapy, his vasoplegic shock improved and he was discharged home.DiscussionPARADIGM-HF found that the introduction of an ARNI in patients with ambulatory symptomatic HFrEF reduces the risk of death and heart failure hospitalization. Most recently, PIONEER-HF showed that ARNI reduced N-terminal pro-B-type natriuretic peptide levels at 4 and 8 weeks, without significantly different rates of medication-related adverse effects. However, thus far, no clinical trials have examined the role of ARNI in CS. Our case report highlights the risk of vasoplegic shock caused by initiation of ARNI in patients hospitalized with CS especially in whom renal and hepatic impairment is present.

Current Perspectives in Management of Edema in Nephrotic Syndrome.

Idiopathic nephrotic syndrome is the most common glomerulopathy in childhood characterised by heavy proteinuria, hypoalbuminemia and edema. Most of the patients have mild and transient edema but those with difficult to treat nephrotic syndrome can develop severe edema which may have serious consequences such as immobility, cellulitis and peritonitis. Understanding of the pathophysiology of edema is still evolving with recent research elucidating newer mechanism of sodium retention through plasmin mediated epithelial sodium channel activation in collecting duct. Patients with mild edema do not require specific diuretic therapy as it improves with steroid induced diuresis. In this review, the authors describe the current perspective in management of moderate to severe edema in childhood nephrotic syndrome including various parameters to assess intravascular volume status which is important for planning overall treatment strategy. Then they briefly discuss about various classes of diuretics, aquaretics and evidence based use of furosemide albumin combination therapy for treatment of edema. Management strategy for a small proportion of patients, who are unresponsive to furosemide therapy, includes diuretic synergism, intravenous furosemide albumin combination therapy and continuous intravenous furosemide infusion.

Effect of diuretic infusion clinic in preventing hospitalization for patients with decompensating heart failure.

Introduction:It is proposed that access to administering intravenous furosemide outside the hospital can contribute to lowering hospital admissions for heart failure. This study aims to evaluate the effect of outpatient furosemide infusion protocol in preventing hospitalization for patients with decompensating heart failure. This constitutes designing a viable clinical pathway in hospitals using a multidisciplinary heart failure program.Methods:A prospective interventional study testing the effect of diuretic infusion clinic in preventing hospitalization for patients with decompensating heart failure was conducted on 150 decompensating heart failure patients requiring hospital admission. Only 105 patients met the criteria and subsequently enrolled in the study. Each patient was administered intravenous furosemide infusion one or more times according to the protocol and depending on their symptoms of decompensation. Patients were referred for admission at any point once there is no improvement of their medical condition, or referred to heart failure clinic when clinical picture improved as observed by the treating team.Results:In total, 14 of 105 patients who received intravenous furosemide infusion did not respond to diuretic infusion protocol and required hospital admission while 91 patients responded to same protocol and did not require admission, P value was statistically significant in three laboratory test measures of potassium (<0.001), urea (0.004), and creatinine (0.008). Heart failure with reduced ejection fraction was observed in 70 (76.9%) responders with a mean ejection fraction of 23% and in 9 (64.3%) non-responders with mean ejection fraction of 19.9%.Conclusion:Outpatient intravenous furosemide infusion protocol is effective in preventing hospitalization for decompensating heart failure and a viable clinical pathway for heart failure programs.

Renal Nerve Deafferentation Attenuates the Fall in GFR during Intravenous Infusion of Furosemide in Anesthetized Rats

Introduction: Furosemide reduces the glomerular filtration rate (GFR) and increases the renal vascular resistance (RVR) despite inhibiting tubuloglomerular feedback but increases proximal tubule pressure, renin release, and renal nerve activity. Objective: This study tested the hypothesis that the fall in GFR with furosemide is due to volume depletion or activation of angiotensin type 1 (AT1) receptors or renal nerves. Methods: Furosemide was infused for 60 min at 1.0 mg·kg⁻¹·h⁻¹ in groups of 5–8 anesthetized rats. Additional groups received intravenous volume replacement to prevent fluid and Na⁺ losses or volume replacement plus losartan or plus sham denervation or plus renal denervation or renal nerve deafferentation. Results: At 60 min of infusion, furosemide alone reduced the GFR (–37 ± 4%; p < 0.01). This fall was not prevented by volume replacement or pretreatment with losartan, although losartan moderated the increase in RVR with furosemide (+44 ± 3 vs. +82 ± 7%; p < 0.01). Whereas the GFR fell after furosemide in rats after sham procedure (–31 ± 2%), it was not changed significantly after prior renal deafferentation. Proximal tubule pressure increased significantly but returned towards baseline over 60 min of furosemide, while urine output remained elevated, and GFR and renal blood flow depressed. Conclusions: The fall in GFR over 60 min of furosemide infusion is independent of volume depletion or activation of AT1 receptors but is largely dependent on renal afferent nerves.

P2593Evaluation of an ambulatory heart failure service - a 2 years' experience

Abstract Background Heart failure accounts for 1–2% of health care expenditure in the National Health Service in the United Kingdom. Approximately 60–70% of that cost is in hospitalization for treatment. Various methods have been employed to reduce hospitalization in chronic heart failure; however effectiveness and safety of these methods have yet to be evaluated. Our ambulatory heart failure unit, run by specialist heart failure nurses, seeks to reduce admissions to hospital for heart failure by administering intravenous (I.V) diuretics in a day unit setting for ambulatory patients. Purpose We have reviewed data from December 2016 to December 2018 of patients using the ambulatory heart failure services in our hospital and evaluated its safety and effectiveness. Methods Retrospective evaluation of data collected from the ambulatory heart failure unit over a 24-month period as well as hospital data on admissions and length of stay of heart failure patients. Qualitative data was also collected from patients using the ambulatory heart failure unit. Results Since the opening of the ambulatory heart failure unit in December 2016, we have had 393 patient episodes. Referrals were largely from the community (265, 67%) however 128 (33%) patients were referred from an inpatient setting. Patients were treated for a mean of 12 days with intravenous furosemide infusion. The minimum dose of furosemide used was 120mg over 1 hour whereas maximum dose was 360mg over 2 hours. This translated into 4351 hospital bed days saved in a 24-month period. 144 (37%) of patients had heart failure with preserved ejection fraction (EF &gt;40%), and 239 (61%) had heart failure with reduced ejection fraction (EF &lt;40%). 28 patients (7%) referred to the unit were deemed inappropriate for unit and required admission. A further 35 patients (9%) were admitted to hospital for other illnesses whilst being treated on the unit due to various reasons. 3 patients (0.8%) died in the community during the period they were receiving care on the unit. Of the 63 patients (16%) admitted to hospital 23 (6%) died during that hospital admission. The number of all cause mortality of our patients was 26 (7%) during the time they were treated on the unit. Whilst the number of heart failure hospital admissions remained similar, the average length of stay in hospital for heart failure dropped by 0.99 days. Patient feedback on the unit was excellent, with patients feeling more independent and in control of their health. Conclusions The ambulatory heart failure unit reduces the burden on the hospital by reducing the length of stay of heart failure patients and may be preferred by patients. Intravenous diuretics on a day case basis are safe, as evident by unchanged overall mortality of heart failure patients.

Early decongestive therapy versus high-flow nasal cannula for the prevention of adverse clinical events in patients with acute cardiogenic pulmonary edema.

Few studies have investigated the role of decongestive therapy and high-flow nasal cannula (HFNC) in preventing reintubation and in-hospital mortality in patients with acute cardiogenic pulmonary edema (ACPE). Data from patients with ACPE who were weaned from mechanical ventilation in the cardiac intensive care unit between January 2013 and December 2017 were retrospectively evaluated. All patients were treated with HFNC or conventional oxygen therapy (COT), such as a nasal cannula or venturi mask, immediately after extubation. Decongestive therapy (intravenous furosemide infusion) was administered at the discretion of the attending physician. Of 212 patients treated during the study period, 47 were excluded due to recent open-heart surgery and two, due to insufficient clinical data. The remaining 163 patients had a mean age of 67.4±14.3 years, and 92 (56.4%) were male; 44 patients received HFNC, and 119 COT. Mean weight loss within 72 hours of extubation was -0.86±2.03 kg. A total of 38 patients (23.3%) required reintubation, 21 of whom (12.9%) required reintubation within 72 hours of extubation. In-hospital mortality occurred in 16 patients (9.8%). Multivariate analysis showed that weight increase within 72 hours of extubation was independent determinants of reintubation (OR =1.7; 95% CI: 1.2-2.2; P<0.001) and in-hospital mortality (OR =1.5; 95% CI: 1.1-2.1; P=0.005). The use of HFNC was not associated with reintubation or in-hospital mortality. Our findings indicate that early weight loss resulted in reduced reintubation and in-hospital mortality in patients with ACPE. However, HFNC and COT did not differ in the prevention of reintubation and in-hospital mortality. Therefore, aggressive decongestive therapy, rather than HFNC, should be considered early after extubation.

Autonomic Cardiovascular Responses to Orthostatic Stress After a Short Artificial Gravity Exposure.

Intermittent artificial gravity (AG) training over days and weeks has been shown to improve the human orthostatic tolerance limit (OTL) and improve cardiovascular regulation in response to orthostatic stress. Effects of a single AG exposure are currently unknown. We tested cardiovascular responses to orthostatic stress in 16 hypovolemic subjects (9 men and 7 women), once following a single, short (∼90 min) bout of AG and once following a similar period of head-down bed rest (HDBR). Hypovolemia was produced by intravenous furosemide infusion (20 mg) and orthostatic stress was produced by combined 70° head-up tilt (HUT) and progressively increasing lower body negative pressure until symptoms of presyncope developed. To assess reflex-induced changes in cardiovascular regulation, heart rate and blood pressure variability were analyzed by spectral analysis and baroreflex activity was evaluated by transfer function analysis. Compared to HDBR, a short AG exposure increased men's low frequency (0.04-0.15 Hz) power of systolic blood pressure (SBPLF), but did not change women's SBPLF responses to orthostatic stress. In response to 70° HUT, compared to supine, low frequency phase delay (PhaseLF) between systolic blood pressure and RR intervals increased by ∼20% following HDBR, but did not change following AG, reflecting improved baroreflex activity at a milder level of orthostatic stress after AG. These results indicate that a short bout of AG increased both sympathetic and baroreflex responsiveness to orthostatic stress in hypovolemia-induced, cardiovascular-deconditioned men and women, which may contribute to the AG-induced improvement of OTL shown in our previous reports.Zhang Q, Evans JM, Stenger MB, Moore FB, Knapp CF. Autonomic cardiovascular responses to orthostatic stress after a short artificial gravity exposure. Aerosp Med Hum Perform. 2017; 88(9):827-833.

Effects of hypertonic saline solution on body weight and serum creatinine in patients with acute decompensated heart failure.

AIMTo test the safety and effectiveness of hypertonic saline solution (HSS + F) as a strategy for weight loss and prevention of further deterioration of renal function.METHODSPatients admitted with acute decompensated heart failure (ADHF) who received HSS + F were included in the study. After a period of a standard ADHF treatment, our patients received an intravenous infusion of furosemide (250 mg) combined with HSS (150 mL of 3% NaCl) twice a day for a mean duration of 2.3 d. Our primary outcomes were weight loss and a change in serum creatinine per day of treatment. The parameters of the period prior to treatment with HSS + F were compared with those of the period with HSS + F.RESULTSA total of 47 patients were included. The mean creatinine on admission was 155 μmol/L ± 65 μmol/L, the ejection fraction was 40% ± 17%. The experimental treatment (HSS + F) resulted in greater weight loss per day of treatment than the standard treatment (-1.4 kg/d ± 1.4 kg/d vs -0.4 kg/d ± 1.0 kg/d, P = 0.0168). Importantly, the change in creatinine was not significantly different.CONCLUSIONThis study supports the effectiveness of HSS + F on weight loss in patients with ADHF. The safety profile, particularly with regard to renal function, leads us to believe that HSS + F may be a valuable option for those patients presenting with ADHF who do not respond to conventional treatment with intravenous furosemide alone.

Immune-Inflammatory and Metabolic Effects of High Dose Furosemide plus Hypertonic Saline Solution (HSS) Treatment in Cirrhotic Subjects with Refractory Ascites.

IntroductionPatients with chronic liver diseases are usually thin as a result of hypermetabolism and malnutrition expressed by reduced levels of leptin and impairment of other adyponectins such as visfatin.AimsWe evaluated the metabolic and inflammatory effects of intravenous high-dose furosemide plus hypertonic saline solutions (HSS) compared with repeated paracentesis and a standard oral diuretic schedule, in patients with cirrhosis and refractory ascites.Methods59 consecutive cirrhotic patients with refractory ascites unresponsive to outpatient treatment. Enrolled subjects were randomized to treatment with intravenous infusion of furosemide (125–250mg⁄bid) plus small volumes of HSS from the first day after admission until 3 days before discharge (Group A, n:38), or repeated paracentesis from the first day after admission until 3 days before discharge (Group B, n: 21). Plasma levels of ANP, BNP, Leptin, visfatin, IL-1β, TNF-a, IL-6 were measured before and after the two type of treatment.ResultsSubjects in group A were observed to have a significant reduction of serum levels of TNF-α, IL-1β, IL-6, ANP, BNP, and visfatin, thus regarding primary efficacy endpoints, in Group A vs. Group B we observed higher Δ-TNF-α, Δ-IL-1β, Δ-IL-6, Δ-ANP, Δ-BNP, Δ-visfatin, Δ-Leptin at discharge.DiscussionOur findings underline the possible inflammatory and metabolic effect of saline overload correction in treatment of cirrhosis complications such as refractory ascites, suggesting a possible role of inflammatory and metabolic-nutritional variables as severity markers in these patients.

31. Differential effects of intravenous bolus furosemide and continuous furosemide infusion on in-hospital management and outcomes among patients admitted with acute decompensated heart failure

Loop diuretics are a cornerstone in the management of Acute Decompensated Heart Failure (ADHF). However, the best therapeutic strategy in terms of intermittent boluses versus continuous infusion is still unclear.We set to examine the differences in hospital management and short-term and long-term mortality of patient receiving furosemide bolus or infusion treatment for ADHF.This is a retrospective cohort study of 207 patients admitted to KKUH with ADHF. Clinical data, labs, in-hospital outcomes and long-term mortality data were collected through review of medical records and HEARTS registry database. We stratified our cohort into two groups; furosemide infusion and bolus groups.The Mean age was 61.5 ± 13.87 years, and 66.2% were males. Approximately 42% had left ventricular ejection fraction LVEF p = 0.033) and anemia (18.1% vs. 4.25, P = 0.006). They had less diabetes (30.6% vs. 38.5%, p = 0.006) and prior MI (18.1% vs. 32.3%, p = 0.006). Infusion group received higher total daily diuretic dose ( p p = 0.002) and mechanical ventilation (11.1% vs. 3.1, p = 0.038). There was no difference in total urine output and renal outcomes between the two groups. The infusion group had longer hospital stay (15.40 ± 12.14 vs. 10.26 ± 6.74 days, p p = 0.002). ADHF patients who received furosemide infusion needed higher diuretic dose, had significantly longer hospital stay and higher long-term mortality.

E2F1-CDK1 pathway activation in kanamycin-induced spiral ganglion cell apoptosis and the protective effect of CR8

Cochlear hair cell loss results in the secondary loss of spiral ganglion cells (SGCs). The death of these SGCs is due to apoptosis. The E2F1-cyclin dependent kinase 1 (CDK1) pathway is believed to represent an important mechanism of neuronal cell death. However, the role of this pathway in spiral ganglion neuronal apoptosis has not yet been reported. In this study, we deafened guinea pigs with a subcutaneous injection of kanamycin followed by an intravenous infusion of furosemide and then assayed the expression levels of cleaved caspase-3, E2F1, CDK1 and cleaved caspase-9 during the induced SGC apoptosis. Our results revealed that co-administration of kanamycin and furosemide rapidly induced hair cell loss in the guinea pigs and then resulted in a progressive loss of SGCs. Expression levels of E2F1 and CDK1 were obviously up-regulated at 1 and 3 days after deafening. Cleaved caspase-9 also increased robustly 1 or 2 weeks after the deafening procedure. The up-regulation of E2F1, CDK1 and cleaved caspase-9 was significantly attenuated by the systemic injection of CR8 (1mg/kg/day, intraperitoneally) starting at 5min after deafening. These findings indicate that the activation of the E2F1-CDK1 pathway and cell cycle re-entry contributes to the apoptosis of SGCs and that the selective inhibition of this signaling cascade may represent an attractive therapeutic strategy. CR8 has the potential to protect SGCs from apoptosis.

Characteristic time courses of cortical and medullary sodium signals measured by noninvasive (23) Na-MRI in rat kidney induced by furosemide.

To characterize regional kidney sodium response by MRI following NKCC2 inhibition. Regional renal sodium signals were monitored noninvasively using (23) Na-MRI at 9.4T with a temporal resolution of 1.5 min in anesthetized rats (N = 14). A mild NKCC2 inhibition was induced using a slow intravenous furosemide infusion. Time course of sodium signal was modeled as an exponential transient with a single characteristic time constant. Under normal physiological conditions, the renal sodium signals in medullary and cortical regions were stable and found to respond differently to furosemide challenge. Furosemide infusion at 1.2 mg/kg/h (N = 7) increased sodium signal in the cortex by 40 ± 6% (P < 7 × 10(-5) ) whereas decreased in the medulla by 29 ± 2% (P < 3 × 10(-6) ) with different temporal kinetics. The characteristic time constants of the change were determined to be: 8 ± 2 and 70 ± 10 min for medulla and cortex. Also, the medullary change occurred 9(±3) times faster than cortical independent of furosemide infusion rate up to 35 mg/kg/h. The pharmacological effects in terms of regional kidney sodium signal changes induced by NKCC2 inhibition are region-specific and highly predictable. Using noninvasive sodium MRI, we obtained regional renal sodium kinetics data sets in response to a low dose furosemide infusion in normal rats.

A prospective, randomized study to evaluate the efficacy of various diuretic strategies in acute decompensated heart failure.

To evaluate the safety and efficacy of various initial strategies of loop diuretic administration in patients with acute decompensated heart failure (ADHF) on diuresis, renal function, electrolyte balance and clinical outcomes. Consecutive patients admitted with ADHF were randomized into three groups - intravenous furosemide infusion+intravenous dopamine, intravenous furosemide bolus in two divided doses and intravenous furosemide continuous infusion alone. At 48h, the treating physician could adjust the diuretic strategy. Primary endpoint was negative fluid balance at 24h after admission. Secondary end points were duration of hospital stay, negative fluid balance at 48, 72, 96h, the trend of serum electrolytes, and renal function and 30 day clinical outcome (death and emergency department visits). Overall ninety patients (thirty in each group) were included in the study. There was a greater diuresis in first 24h (p=0.002) and a shorter hospital stay (p=0.023) with the bolus group. There was no significant difference in renal function and serum sodium and serum potassium levels. There was no difference in the number of emergency department visits among the three groups. All three modes of diuretic therapies can be practiced with no difference in worsening of renal function and electrolyte levels. Bolus dose administration with itsrapid volume loss and shorter hospital stay might be a more effective diuretic strategy.