重组人脑钠肽对慢性心衰犬血流动力学和肾功能的影响

目的研究国产重组人脑钠肽(rhBNP)对慢性心衰犬血流动力学及肾功能的影响。方法用右心室快速起搏(RVP)或狭窄下腔静脉(TIVCC)形成犬的心衰模型。结果RVP心衰犬iv rhBNP后,平均动脉压(MAP)、左室内压(LVSP)、LVdp/dt、肺动脉压(PAP)、左室舒张末期压(LVEDP)、总外周阻力(TPR)及肾血管阻力(RVR)呈剂量依赖性下降,LVdp/dt/P、左室做功(LVW)、心输出量(CO)和心率(HR)无明显改变;TIVCC心衰犬在iv同剂量rhBNP后,MAP,LVEDP和CO下降,其他心功能指标无明显改变。两种心衰犬给药后尿量和尿钠排出量均增加。结论rhBNP有舒张血管和利尿作用,能明显降低心衰犬的心脏前后负荷,不影响心脏收缩功能。     

重组人脑利钠肽对急性心力衰竭患者血流动力学指标的影响分析

目的 分析重组人脑利钠肽(BNP)对急性心力衰竭(AHF)患者血流动力学指标的影响.方法 86例AHF患者,以随机双盲法分为参照组和实验组,各43例.参照组采用常规治疗,实验组在参照组基础上采用重组人脑利钠肽治疗.对比两组临床疗效、心功能指标、血流动力学指标、血清炎症因子.结果 实验组临床总有效率95.35％ 明显高于...     

重组人脑利钠肽(rhBNP)治疗慢性心衰的临床观察

目的 分析rhBNP对慢性充血性心力衰竭疗效的影响.方法 选取慢性心力衰竭患者 40 例,随机分为对照组和观察组各 20例.对照组治疗给予强心、利尿、A CE I 药物; 观察组在对照组治疗的基础上加用新活素(rhBNP),疗程均为10 d.结果 观察组心功能改善情况、总有效率优于对照组(P<0.05); 治疗前后的心率,左心室射血分数(LV EF) 观察组均优于对照组(P< 0.05).结论 新活素(rhBNP)可显著改善慢性心力衰竭患者的心功能和临床症状,提高患者的生活质量.     

重组人脑利钠肽安全药理学研究

目的:观察重组人脑利钠肽(rhBNP)对大鼠心血管、呼吸系统和对小鼠神经系统的影响。方法:大鼠实验分低、中、高3个剂量及空白对照共4个组,给药组分别单次静脉注射(iv)rhBNP 22．5,45．0和90．0μg·kg~(-1),对血压、心电图(ECG)、呼吸频率及节律进行观察。小鼠实验分低、中、高3个剂量及空白对照共4个组,给药组分别单次iv rhBNP 45．0,90．0和180．0μg·kg~(-1),对动物自发活动和爬杆能力进行观察。结果:rhBNP使大鼠收缩压、舒张压、平均动脉压降低,且存在量效关系,2h内上述指标基本恢复正常,对心率、心律、ECG之QRS时间、T波、ST段、呼吸频率、节律和幅度无明显影响。对小鼠自发活动和爬杆能力无明显影响。结论:rhBNP对心血管系统有一定影响,可使收缩压、舒张压、平均动脉压降低。     

重组人脑钠肽对慢性心力衰竭兔的实验研究

目的研究重组人脑钠肽（rhBNP）对慢性心力衰竭（CHF）兔血流动力学及心功能的影响。方法用导管捅破兔主动脉瓣,导致超容量负荷型兔的心衰模型。造模成功后动物饲养约5周。心力衰竭兔随机分为三组,分别给予rhBNP、硝普钠和安慰剂（5%葡萄糖）静脉滴注。采用心脏超声图观察用药前后心功能指标。1周后静脉给予同样三种药物,观察用药前后HF兔血流动力学参数的变化。结果HF兔静脉滴注rhBNP后心脏超声检查示LVEF较治疗前明显升高（P〈0.05）,LVEF从（0.63±0.06）L上升至（0.70±0.07）L（P〈0.05）;CO无明显变化;LVESV、LAD较治疗前下降明显（P〈0.05）,LVESV从（2.1±0.7）m l降至（1.2±0.9）m、lLAD由（11.0±1.9）mm下降至（10.1±1.8）mm。而硝普钠治疗组和安慰剂组上述参数无明显变化（P〉0.05）。血流动力学监测：给药3 h后三组比较发现：rhBNP组LVEDP、MAP和DBP下降差异具有统计学意义,LVEDP从（19.1±2.8）mm Hg下降至（6.4±5.9）mm Hg（P〈0.05）;DBP从（72.6±6.3）mm Hg降至（64.6±6.1）mm Hg（P〈0.05）;硝普钠组SBP、DBP、MAP、LVSP、LVEDP均明显下降（P〈0.05）,而且以LVSP和SBP下降最为显著;安慰剂组上述参数无明显变化。结论慢性HF兔应用rhBNP后可以增加LVEF,缩小LVESV和LAD。rhBNP能明显降低慢性HF兔的心脏前后负荷,使DBP、MAP明显下降,尤其是LVEDP下降显著。     

重组人脑钠肽对急性心衰患者心肾功能及脑利钠肽的影响

目的 探讨重组人脑钠肽对急性心衰患者心肾功能及脑利钠肽（BNP）的影响。方法 选取2011年1月-2016年12月郑州市第七人民医院收治的急性心力衰竭患者120例。随机分为两组,对照组在常规治疗的基础上给予硝普钠,观察组在常规治疗的基础上给予重组人脑钠肽。用药48 h后,观察两组患者的心功能改善情况、左心室射血分数、血浆BNP水平、排尿量、血肌酐、血钾浓度变化情况。结果 用药后48 h,观察组心功能改善的总有效率为83.34%,显著优于对照组的56.67%,差异有统计学意义（P<0.05）。与用药前相比,两组患者用药后LVEF均明显的升高,组内差异有统计学意义（P<0.05）;且观察组明显高于对照组,差异有统计学意义（P<0.05）;用药后两组的血浆BNP水平均明显降低,组内差异有统计学意义（P<0.05）,且观察组明显低于对照组,差异有统计学意义（P<0.05）;用药后两组的尿量均明显增加,组内差异有统计学意义（P<0.05）;且观察组的多于对照组,差异有统计学意义（P<0.05）。与用药前相比,两组患者的血肌酐浓度均轻度升高,观察组血钾浓度轻微升高,对照组血钾浓度轻微下降,差异均无统计学意义;停药后,未见进一步加剧。结论 应用重组人脑钠肽治疗急性心力衰竭患者,可以改善患者的心功能情况,降低血浆BNP水平,利尿,对肾功能未见不良影响。     

重组人脑利钠肽对急性心力衰竭患者血流动力学、心功能和免疫功能的影响

目的 观察临床中应用重组人脑利钠肽对急性心力衰竭患者的血流动力学、心功能以及免疫功能的影响。方法 选取南平市第一医院2011年6月至2013年6月收治的112例急性心力衰竭患者,随机分为研究组与常规组,均56例。常规组应用临床常规治疗,研究组在常规治疗基础上应用重组人脑利钠肽,观察两组患者血流动力学和心功能以及免疫功能的变化。结果 治疗后研究组和对照组HR比较差异有统计学意义(P<0.05)。治疗后研究组与对照组左心室收缩末期容积(ESV)、左室射血分数(LVEF)、左心室舒张末期容积(EDV)较治疗前有明显的改善,且组间的数据比较差异有统计学意义(P<0.05)。治疗后研究组CD3、CD4、CD4/CD8较治疗前有明显的改善,且研究组优于对照组(P<0.05),差异有统计学意义。结论 应用重组人脑利钠肽可以改善急性心力衰竭患者的血流动力学指标,并对其心肌功能起到保护作用,增强其机体的免疫功能,值得临床中应用。     

重组人脑利钠肽对慢性心力衰竭患者炎症因子及血流动力学的影响

慢性心力衰竭（CHF）是临床极为常见的危重症,是所有不同病因器质性心脏病的主要并发症。近年来虽然一些重要的心血管疾病（冠心病、高血压及瓣膜病等）的发病率和病死率有所控制,但心力衰竭的发病率却日益增高。研究表明,炎症细胞因子异常在慢性心力衰竭（CHF）的发病机制中起着重要的作用。     

重组脑钠肽对顽固性心衰伴肾功能不全病人血流动力学及肾功能影响

目的观察应用重组脑钠肽(rhBNP)治疗顽固性心力衰竭伴肾功能不全病人的血流动力学及肾功能变化。方法应用rhBNP治疗10例顽固性心力衰竭伴肾功能不全病人,应用时放置Swan-Ganz漂浮导管进行血流动力学监测,测定病人的动脉血压、中心静脉压(CVP)、右房压(RAP)、肺毛细血管楔压(PCWP)等。检查病人的左室射血分数(EF)、肾功能,计算出病人的肌酐清除率(Ccr),应用rhBNP后24,48 h再次复查上述指标。结果静脉应用rhBNP后病人的PCWP在5 min时降低(3.0±s 0.8)mmHg,60 min时降低(14.0±2.6)mmHg,降低了27%,以后降幅趋于平稳,至24 h及48 h时PCWP稳定在(30±5)mmHg。静脉应用rhBNP后48 h,PCWP降低了(19.4±2.2)mmHg,占38.8%,主要发生在应用后的1 h以内,占总下降率的64.4%,同时RAP及CVP也有所下降。EF 48 h内有明显上升,从(30±6)%到(39±7)%,P<0.01。但动脉血压无明显变化。病人Ccr有明显变化:从(27±17)mL·min~(-1)上升到(35±17)mL·min~(-1),P<0.01。结论顽固性心力衰竭时应用rhRNP静脉注射可快速、有效地降低PCWP,并改善肾功能,从而有效地治疗顽固性心力衰竭。     

重组人脑钠肽预防对比剂肾病的效果

目的探讨重组人脑钠肽对对比剂肾病的预防效果。方法将76例冠心病合并肾功能不全患者完全随机分为常规治疗组（35例）和重组人脑钠肽组（41例）,常规治疗组在常规治疗基础上仅生理盐水水化;重组人脑钠肽组在常规治疗及水化基础上,应用重组人脑钠肽,剂量为1．5μg/kg,3min后以0．015μg／（kg·min）微量泵静脉持续泵人24h。观察2组患者治疗前及经皮冠状动脉介入（PCI）48h后的cr及胱蛋白酶抑制素C（CysC）水平,并比较2组对比剂肾病的发生率。结果入院时常规治疗组和重组人脑钠肽组患者cr及CysC水平差异无统计学意义[分别为（214±78）μmol／L比（224±83）μmol／L,（1．63±0．32）mg／L比（1．71±0．33）mg／L;P〉0．05];常规治疗组PCI48h后cr及CysC水平明显高于入院时水平及重组人脑钠肽组PCI48h后[分别为（285±92）μmol／L比（214±78）、（220±80）μmol／L,（3．41±0．67）mg／L比（1．63±0．32）、（1．65±0．29）mg／L;均P〈0．05]。常规治疗组对比剂肾病的发生率明显高于重组人脑钠肽组[85．7％（30／35）比12．2％（4／41）,P〈0．05]。结论重组人脑钠肽可预防对比剂。肾病的发生。     

RENAL DENERVATION POTENTIATES THE NATRIURETIC AND DIURETIC EFFECTS OF ATRIAL NATRIURETIC PEPTIDE IN ANAESTHETIZED RABBITS

1. The role of the renal nerves in modulating the action of atrial natriuretic peptide (ANP) in the kidney was studied by comparing the responses to ANP in innervated and surgically denervated kidneys in anaesthetized rabbits. 2. A low dose of ANP (0.05 μg/kg per min, i.v.) was used to minimize the confounding effects of systemic hypotension. 3. The natriuretic and diuretic responses to ANP were significantly greater in denervated kidneys than in kidneys with intact innervation. Sodium excretion from denervated kidneys rose by 7.49 ± 3.11 μmol/min in response to ANP (-55%, P<0.05) compared to 0.84 ± 0.59 μmol/min (-28%, NS) in innervated kidneys. Urine flow increased markedly in denervated kidneys by 73.2 ± 29.9 μmol/min (-60%, P<0.05) but not in innervated kidneys. 4. Fractional sodium excretion increased significantly in denervated kidneys in response to ANP (median 2.3% to median 3.0%, P<0.05). 5. Renal blood flow, glomerular filtration rate (GFR) and glomerular capillary pressure were unchanged in response to ANP in either denervated or innervated kidneys. Pre-glomerular vascular resistance fell in denervated kidneys during ANP infusion. 6. The natriuresis and diuresis observed in the denervated kidneys, due to an increased fractional excretion of sodium without increases in GFR or glomerular capillary pressure, is consistent with effects of ANP on tubular reabsorption of sodium. 7. Thus, ANP produced a natriuresis and diuresis at a low dose in denervated but not in innervated kidneys. This indicates that reflex activation of renal nerves may antagonize the renal effects of ANP.     

山莨菪碱对麻醉犬血流动力学及心泵功能的影响

以心阻抗血流图测定麻醉犬的心输出量及心缩时间间距,同时测定动脉血压,观察了山莨菪碱对犬血流动力学和心泵功能的影响。山莨菪碱5mg/kg wt,iv后5～10min,平均动脉压和总外周阻力有显著下降(两者P<0.001),心率和心输出量也有一定程度的减少(两者分别为P<0.002和P<0.05):Q-Z间期延长(P<0.05),Heather指数降低(P<0.05),PEP/LVET增大(P<0.02),与给药前的对照状况相比差异有高度显著性或显著性。给药后60～90min上述指标大致恢复到对照水平。结果表明:山莨菪碱在扩张血管、降低总外周阻力、降低动脉血压的同时,还降低心脏的泵血功能。     

RENAL INTERACTION OF ATRIAL NATRIURETIC PEPTIDE WITH ANGIOTENSIN II: GLOMERULAR AND TUBULAR EFFECTS

1. The possible interactions between the renal effects of atrial natriuretic peptide (ANP) and angiotensin II (AII) were studied in normal sodium-replete human subjects. Recent investigations have suggested that ANP inhibits the pressor and volume-retaining effects of activation of the renin-angiotensin system. Thus, ANP may attenuate the effects of AII on renal haemodynamics or tubular transport. 2. ANP (0.1 micrograms/kg per min, 60 min) was intravenously infused into eight normal human subjects with and without pretreatment with enalapril (20 mg, per oral), an inhibitor of the converting enzyme, and during infusion of AII (10 mg/kg per min). 3. ANP infusion alone caused increases in the urine volume (from 96 +/- 23 to 229 +/- 44 mL/h, P less than 0.05) and urinary sodium excretion (from 11.5 +/- 1.6 to 20.9 +/- 4.2 mEq/h, P less than 0.05). These changes were accompanied by an increase in the glomerular filtration rate (from 127 +/- 9 to 158 +/- 9 mL/min, P less than 0.05). ANP infusion after enalapril administration lowered the mean blood pressure (from 76 +/- 2 to 71 +/- 3 mmHg, P less than 0.05) to a level similar to that observed during ANP infusion alone (from 84 +/- 2 to 74 +/- 2 mmHg, P less than 0.01), but did not result in a significant diuresis (from 139 +/- 23 to 174 +/- 51 mL/h) or natriuresis (from 19.7 +/- 2.5 to 14.3 +/- 3.4 mEq/h, P less than 0.05). This combined treatment with a converting enzyme inhibitor and ANP reduced both the glomerular filtration rate (160 +/- 9 to 141 +/- 10 mL/min) and the renal plasma flow (from 775 +/- 49 to 570 +/- 45 mL/min, P less than 0.01). 4. The antinatriuretic effects of exogenous AII were reversed by superimposed ANP infusion (urinary sodium excretion: from 4.8 +/- 1.0 to 24.3 +/- 5.2 mEq/h, P less than 0.01). Under these conditions, the glomerular filtration rate increased (from 114 +/- 6 to 156 +/- 7 mL/min, P less than 0.05) to levels similar to those observed with ANP infusion alone. In addition the increased tubular sodium reabsorption induced by AII was inhibited by concomitant ANP infusion (fractional proximal tubular sodium reabsorption: from 90.7 +/- 3.5 to 80.3 +/- 16.6%, P less than 0.05, fractional post-proximal tubular sodium reabsorption: from 91.5 +/- 9.8 to 87.6 +/- 8.8%, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

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 μg/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 μg/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.     

NATRIURETIC AND HYPOTENSIVE EFFECTS OF BRAIN NATRIURETIC PEPTIDE IN ANAESTHETIZED DOCA-SALT HYPERTENSIVE RATS

1. Both natriuretic and hypotensive effects of brain natriuretic peptide (BNP), a novel peptide identified in porcine brain, were investigated in anaesthetized DOCA-salt rats and control rats. 2. An intravenous injection of two different doses (0.5 and 5.0 nmol/kg) of BNP produced a rapid and marked natriuresis and hypotension in DOCA-salt rats. 3. In particular, significant differences of responsiveness were observed between DOCA-salt and control rats when administered the lower dose of BNP. 4. It was suggested that DOCA-salt rats might be relatively more susceptible to BNP.     

RENAL EXTRACTION OF ATRIAL NATRIURETIC PEPTIDE IN UNILATERAL RENAL ARTERY STENOSIS

1. Elevated peripheral atrial natriuretic peptide (ANP) levels were observed in 12 patients with unilateral renal artery stenosis (U-RAS). 2. Renal extraction of ANP was higher across the affected than the unaffected kidney in U-RAS, provided the glomerular filtration rate in the affected kidney was not severely reduced (> 12 mL/min). As ANP is a high clearance compound, reduced flow on the affected side may result in increased renal extraction of ANP. 3. When glomerular filtration rate (GFR) in the affected kidney was severely reduced (<12 mL/min), renal extraction of ANP was also reduced, possibly contributing to increased circulating ANP levels in this subgroup. 4. Overall, renal extraction of ANP was inversely correlated to peripheral ANP levels in patients with U-RAS. This might be explained by progressive sodium retention as GFR falls leading to volume expansion and increased ANP secretion.     

IN VIVO AND IN VITRO EFFECTS OF ATRIAL NATRIURETIC PEPTIDE ON RENIN RELEASE

1. This study investigated the effect of atrial natriuretic peptide on renin release from the kidney. The in vitro direct effect was examined in the animal experiment using renal cortical slices of rat, and the in vivo effect was observed in the human infusion study. 2. In the in vitro experiments, alpha-human atrial natriuretic peptide (alpha-hANP) ranging 10(-9) to 10(-6) mol/L did not change the basal renin release rate from the renal cortical slices (-9% at 10(-6) mol/L, NS). Isoproterenol (10(-6) mol/L) increased renin release by 40% (P < 0.001), whereas angiotensin II (10(-6) mol/L) suppressed it by 48% (P < 0.001). However, alpha-hANP did not affect the stimulative effect of isoproterenol or the inhibitory effect of angiotensin II. 3. Also in the human study, infusion of 25 ng/kg per min alpha-hANP failed to change the plasma renin activity in normotensive subjects (-4%) or patients with essential hypertension (+5%), or even in patients with raised renin levels such as renovascular hypertension (+10%) or congestive heart failure (-13%). 4. These results put forth negative views on the direct involvement of atrial natriuretic peptide in renin release from the juxtaglomerular apparatus.     

COMPARISON OF THE EFFECTS OF OUABAIN AND BRAIN NATRIURETIC PEPTIDE IN SALINE-LOADED SHEEP

1. It has been claimed that ouabain is an endogenous hormone that may be pivotal in the pathogenesis of some forms of hypertension and may exaggerate natriuresis in situations characterized by volume overload. We compared the haemodynamic, renal and endocrine effects of ouabain (at approximately 187 ng/kg per min for 2 h) with those of brain natriuretic peptide (BNP; at 5 pmol/kg per min for 2 h) in nine saline-loaded sheep in a balanced, randomized, single-blind, placebo-controlled crossover study. 2. Brain natriuretic peptide infusion reduced mean arterial pressure whereas ouabain infusion caused no change. Haematocrit rose steadily during BNP infusion but fell during ouabain infusion. Neither ouabain nor BNP affected urine volume, sodium, potassium or creatinine excretion. Mean heart rate declined during the ouabain and placebo infusions, but was not altered during BNP infusion. Endogenous ouabain concentrations were not detectable at baseline or during BNP or placebo infusions, but rose to concentrations of 11 ± 1.3 nmol/L during the ouabain infusion. 3. These results suggest that ouabain is not an endogenous hormone present at physiologically relevant concentrations. Furthermore, ouabain does not cause natriuresis during saline-loading in sheep and is therefore unlikely to be responsible for the exaggerated natriuresis seen in some forms of hypertension.