Furosemide-related thiamine deficiency in hospitalized hypervolemic patients with renal failure and heart failure

BackgroundWe aimed to describe the thiamine status in hospitalized hypervolemic heart failure (HF) and/or renal failure (RF) patients treated with furosemide and to investigate whether there was a difference in furosemide-related thiamine deficiency between patients with RF and HF.MethodsPatients who were diagnosed as hypervolemia and treated with intravenous furosemide (at least 40 mg/day) were included in this prospective observational study. Whole blood thiamine concentrations were measured 3 times during hospital follow-up of patients.ResultsWe evaluated 61 hospitalized hypervolemic patients, of which 22 (36%) were men and 39 (64%) were women, with a mean age of 69.00 ± 10.39 (45–90) years. The baseline and post–hospital admission days 2 and 4 mean thiamine levels were 51.71 ± 20.66 ng/ml, 47.64 ± 15.43 ng/ml and 43.78 ± 16.20 ng/ml, respectively. Thiamine levels of the hypervolemic patients decreased significantly during the hospital stay while furosemide treatment was continuing (p = 0.029). There was a significant decrease in thiamine levels in patients who had HF (p = 0.026) and also, thiamine was significantly lower in HF patients who had previously used oral furosemide before hospitalization. However, these findings were not present in patients with RF.ConclusionsThiamine substantially decreases in most hypervolemic patients receiving intravenous furosemide treatment during the hospital stay. Thiamine levels were significantly decreased with furosemide treatment in especially HF patients, but the decrease in thiamine levels did not detected at the same rate in RF patients. Diuretic-induced thiamine loss may be less likely in RF patients, probably due to a reduction in excretion.     

静脉滴注呋塞米治疗难治性充血性心力衰竭的疗效评价

目的 :评价呋塞米静脉滴注治疗难治性充血性心力衰竭 (CHF)的疗效。方法 :常规治疗加静脉注射呋塞米效果差的CHF 2 3例 ,继用呋塞米静脉滴注 5d ,观察其利尿效应 ,监测治疗前后血压、电解质、心率及体重。治疗过程中适当补充钠、钾和维持血压。结果 :静脉滴注呋塞米后每日尿量较治疗前明显增加 (P <0 .0 1) ;第 2、3、4、5天静脉滴注呋塞米量明显少于静脉滴注前 1天和静脉滴注第 1天剂量 (P <0 .0 5 <0 .0 1) ;治疗后心率、体重及血压显著降低 (P <0 .0 1,<0 .0 1,<0 .0 5 ) ,治疗前后血清钾和钠无明显改变 (均P >0 .0 5 )。治疗后所有患者临床症状和体征明显改善。结论 :在常规治疗下加用静脉滴注呋塞米治疗难治性CHF是一种安全有效的方法。     

呋塞米联合小剂量多巴胺间歇静脉泵入治疗终末期心力衰竭合并利尿剂抵抗

目的观察比较间歇微量泵静脉泵入呋塞米和多巴胺与分次静脉推注呋塞米治疗终末期心衰伴利尿剂抵抗患者的疗效。方法将56例利尿剂抵抗性心力衰竭患者随机分为两组,对照组28例患者在进行常规抗心力衰竭治疗基础上,单纯分次静脉推注呋塞米治疗;观察组28例患者在常规抗心力衰竭治疗的基础上同时给予呋塞米和多巴胺间歇静脉泵入治疗。两组患者均治疗5 d。观察治疗前后两组患者在心功能分级（NYHA）、心功能指标、肾功能、尿量和体重等方面的变化。结果与对照组比较,观察组患者心功能分级（NYHA）明显改善,LVEF增加,6 min步行试验距离延长,尿量明显增加（P均〈0.05）。结论对终末期心衰伴利尿剂抵抗的患者,间歇静脉泵入呋塞米和多巴胺治疗的疗效优于单纯静脉推注呋塞米治疗。     

呋喃苯胺酸在人体内的药动—药效学研究

本文研究了利尿药呋喃苯胺酸(速尿) 在人体内的药动—药效学。4名健康受试者分别口服了5,10,20及40 mg剂量的呋喃苯胺酸,测定了各时间的尿药数据,利尿量以及钠与钾离子排泄的增量。实验数据用电子计算机作了非线性最小二乘法模型嵌合处理,表明该药在体内符合双室开放模型。3 h内的总利尿量、总Na⁺+K⁺的排泄增量与给药剂量的对数之间呈现良好的线性关系。给药后各时间的累积尿药量与累积药效之间符合Hill方程式。还推出了该药的排泄速度与利尿速度之间的一个关系式,与实验数据十分吻合。     

Effects of furosemide and bendroflumethiazide on saliva flow rate and composition

Aim of this study was to evaluate the effect on saliva flow rate and composition and on perceived xerostomia. The study used a Latin square design, all subjects being once daily (at 7.00 a.m.) taking the bendroflumethiazide (2.5 mg), furosemide (40 mg), or placebo, in a randomised order. Each treatment period of 7 days was separated by wash-out periods of 14 days. Unstimulated and paraffin chewing stimulated whole saliva, and 3% citric acid stimulated parotid and submandibular-sublingual secretion were collected twice daily, at 7.30 a.m., with the patients in a fasting condition (morning values), and at 10.30 a.m., about 2 h after intake of a standard breakfast (lunchtime values), on day 0 (baseline), day 1 (acute treatment), and day 7 (chronic treatment). Saliva flow rates were measured and all four secretions were analysed for the concentration of sodium, potassium, chloride, and total protein. Xerostomia was assessed by means of a Visual Analogue Scale. Statistical analysis used the Wilcoxon signed rank test. For flow rate, only that of submandibular-sublingual secretion was affected, significantly so in the morning during chronic treatment with both drugs. In resting whole saliva the output of both sodium and chloride tended to decrease especially during treatment with bendroflumethiazide, while in submandibular-sublingual secretion the output of all the electrolytes was decreased, especially for potassium and chloride and during treatment with furosemide. Further, xerostomia tended to increase during treatment with furosemide, statistically significant at lunchtime during chronic treatment. In conclusion, this study has demonstrated a modest effect on salivary flow rate and a more pronounced effect on saliva composition, especially in submandibular-sublingual secretion during treatment of healthy volunteers with therapeutic doses of two different diuretics, encouraging clinical studies in hypertensive patients and basic research as to the presence of a thiazide sensitive Na-Cl cotransporter in human salivary glands.     

Calcium-activated potassium channels in the luminal membrane of Amphiuma diluting segment: voltage-dependent block by intracellular Na+ upon depolarisation

Calcium-activated potassium channels in the luminal membrane of Amphiuma diluting segment were studied using the patch-clamp technique in both the cellattached and inside-out configurations. The open probability (P _o) of the channel is sensitive to both membrane potential and cytoplasmic calcium activity; depolarizing potenials and high calcium concentrations leading to an increased P _o. In the cell-attached condition, channel openings were observed between pipette potentials of –100 and –240 mV. As the driving force for potassium exit from the cell into the pipette is increased the single channel currents show a biphasic response. First, the currents increase as expected; however, the single channel currents diminish in magnitude at pipette potentials more negative than –120 mV. We propose that this reduction is due to rapid blockade of the potassium channel by intracellular sodium.This proposal is supported by two facts: (a) using inside-out patches it was possible to reduce the single channel currents in a concentration- and voltage-dependent manner, similar to that observed in the cell-attached condition, by raising the sodium concentration of the fluid bathing the cytoplasmic face of the patch; (b) pretreatment of tubules with the loop-acting diuretic furosemide (10^–5M), an agent known to decrease the intracellular sodium activity, caused an attenuation of the reduction in single channel current seen under control conditions. Given the very low P _o of the channels at the resting membrane potential and the sensitivity of the channels to intracellular sodium, it is unlikely that blockade of these channels by intracellular sodium would lead to a physiological regulation of the apical K conductance.     

Effects of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection

Summary The goal of this study was to quantitate the effect of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection. The study was carried out on low and normal salt intake to assess potential interaction with salt balance. Eighteen healthy normotensive volunteers were examined in a double placebo-controlled parallel group design. Subjects were randomly put on either low-salt (20 mmol/day) or normal-salt (110 mmol/day) diet. In either arm of the diet volunteers were first treated orally with placebo for 1 week and subsequently with 2.5 mg/day of the angiotensin-converting enzyme inhibitor cilazapril for another 1 week. Cumulative 24-h urinary sodium excretion was measured on the 6th day of the respective week after sham injection and on the 7th day after injection of 40 mg furosemide. Compared to pretreatment with placebo, pretreatment with cilazapril resulted in a higher cumulative sodium excretion after furosemide injection (day 7) than after the sham injection (day 6) on both salt intakes. The difference in natriuresis (cilazapril versus placebo) was evident 2 and 3 h after injection of furosemide. Neither the time of onset nor the magnitude of antinatriuresis were affected by cilazapril. Following furosemide angiotensin II increased significantly even after cilazapril pretreatment. Cilazapril tended to reduce urinary furosemide excretion. At any given urinary furosemide concentration, the increment in urinary sodium excretion was significantly greater with cilazapril irrespective of salt intake. The study shows that (a) cilazapril increases furosemide-induced natriuresis irrespective of salt intake, (b) antinatriuresis is not affected by cilazapril, and (c) angiotensin II levels rise after furosemide on cilazapril in therapeutic doses.Abbreviation ACE angiotensin-converting enzyme     

Preliminary characterization of an Na,K,Cl co-transport activity in cultured human astrocytes

We have studied the potassium uptake using ⁸⁶Rb⁺ into monolayers of secondary cultures of human astrocytes prepared from cerebral hemispheres of a 4-month-old fetus. With the use of inhibitors we could attribute 30–40% of the ⁸⁶Rb⁺ uptake to an Na⁺,K⁺-ATPase, 50–60% to an anion-cation co-transporter and 10% to potassium leak channels. The anion-cation co-transporter was dependent on the simultaneous presence of both sodium and chloride in the incubation medium and is therefore most likely an Na⁺,K⁺,Cl⁻ co-transporter. This is the first evidence of such an Na⁺,K⁺,Cl⁻ co-transport in human astrocytes.     

呋塞米输注方式对肝移植术中肾功能的影响

目的比较术中应用分次输注和连续输注呋塞米对肝移植手术患者围术期肾功能的影响。方法合并不同程度肾功能受损的肝移植患者30例,根据术中输注呋塞米的方式不同均分为分次输注组(A组)和微泵输注组(B组)。记录术中血肌酐(Scr)、尿素氮(BUN)、内生肌酐清除率(Ccr)和尿量的变化。结果与术前比较,无肝期后A组Scr、BUN显著升高(P<0.01),新肝期30min至术后24hCcr显著降低(P<0.01);B组Scr、BUN仅在新肝期30min显著升高(P<0.01),Ccr在无肝期30min和新肝期30min明显降低(P<0.01)。结论微泵输注呋塞米较分次输注更有利于术前肾功能受损患者肝移植术中的肾功能保护。