Therapeutic use of dopamine and beta-blockers modulates plasma interleukin-6 levels in patients with congestive heart failure

We previously reported that the spillover of interleukin-6 (IL-6) into the peripheral circulation increases with the severity of congestive heart failure (CHF), and that the increase is mainly associated with activation of the endogenous sympathetic nervous system. However, the role of the sympathetic nervous system in the increase of IL-6 in CHF patients is not yet fully understood. To address this question, we measured plasma IL-6 levels before and after therapeutic administration of dopamine and betablockers in patients with CHF. After more than 24 h (mean, 34 h) of treatment with a low dose of intravenous dopamine (mean, 2.4 microg/kg/min) in 1 patients with dilated cardiomyopathy and deterioration of CHF, the plasma IL-6 level was increased significantly (30.8 vs. 16.6 pg/ml; p = 0.003) despite the improved hemodynamics. After 377 days of beta-blocker therapy in 24 patients with dilated cardiomyopathy, the plasma IL-6 level was decreased significantly (2.04 vs. 3.11 pg/ml; p = 0.01) along with the improvement of symptoms, left ventricular ejection fraction, and neurohumoral factors. Dopamine increases and beta-blockers decrease the plasma IL-6 level in patients with CHF, suggesting that drugs modulating the sympathetic nervous system may alter IL-6 in these patients.     

依那普利对充血性心力衰竭患者血循环内皮细胞及脑钠素的影响

目的探讨充血性心力衰竭(CHF)时血循环内皮细胞(CEC)计数、血浆脑钠素(BNP)、血浆内皮素(ET-1)及6酮前列腺素F1α(6-Keto-PGF1α)水平的变化及依那普利的干预效应。方法25例CHF患者服用依那普利2周,并检测用药前后自身外周血循环CEC数量、血浆ET-1、BNP及6-Keto-PGF1α的含量,20名健康体检者为对照组。结果CHF患者CEC数量、血浆ET-1及BNP水平明显增高。6-Keto-PGF1α明显减少(P<0.01)。依那普利治疗可使CEC数量、血浆ET-1及BNP水平明显降低及6-Keto-PGF1α含量明显增加(P<0.01)。结论心力衰竭时存在血管内皮细胞受损,而依那普利具有保护血管内皮细胞及改善心功能的作用。     

Effects of diltiazem on down-regulation of lymphocyte beta-adrenoceptors in patients with chronic congestive heart failure

AIM: To determine whether diltiazem could reverse down-regulation of lymphocyte beta-adrenoceptor (beta-AR) in patients with chronic congestive heart failure (CHF). METHODS: Before and after the treatment with diltiazem in CHF patients, lymphocyte beta-AR density was measured with [3H]dihydroalprenolol radioligand binding assay, levels of free cytosolic calcium ([Ca2+]i) in platelets were estimated with fluorescent indicator Fura 2-AM, plasma norepinephrine (NE) levels were measured with 125I-radioimmunoassay. RESULTS: Lymphocyte beta-AR density was lower and [Ca2+]i in platelets was significantly higher in CHF patients than those in control. Plasma NE levels were higher in CHF patients than those in control. Diltiazem therapy reduced [Ca2+]i in platelets and increased lymphocyte beta-AR density in CHF patients without significant change of plasma NE concentration. CONCLUSIONS: Diltiazem partly reversed down-regulation of lymphocyte beta-AR density in CHF patients, and this effect was not related to the level of plasma NE, and might be attributed to intracellular [Ca2+]i decrease.     

氨力农治疗心力衰竭的疗效

目的：观察氨力农治疗心力衰竭（心衰）的临床疗效。方法：３６例心衰的病人，男性２４例，女性１２例；年龄５４±ｓ１４ａ，分为２组，其中３２例给氨力农０．５～１．０ｍｇ／ｋｇ用０．９％氯化钠注射液稀释至１０～２０ｍＬ，静脉注射，５～１０ｍｉｎ注射完，继以５～１０μｇ／ｋｇ氨力农用０．９％氯化钠注射液稀释至１８０ｍＬ，静脉滴注（静滴）６ｈ，共１０ｄ为治疗组；另１６例为用０．９％氯化钠注射液作为安慰剂对照组（其中１２例为安慰剂治疗无效后改为氨力农组），用药方法同治疗组。结果∶氨力农组治疗后总有效率９１％（２９／３２），对照组全部无效，组间比较Ｐ＜０．０１。氨力农组６例于用药ｄ１０的药前及药后２ｈ测血药浓度，发现有效血药浓度为１．１～３．２１μｇ／ｍＬ。结论：氨力农对慢性难治性心衰有效且安全。     

Effects of nitroglycerin ointment on plasma norepinephrine and cyclic nucleotides in congestive heart failure

To assess the effects of nitroglycerin ointment (NTG) on hemodynamics and autonomic nervous activity, 17 normal subjects and 13 patients with severe congestive heart failure (CHF) were studied. In 12 normal subjects, NTG significantly increased the plasma norepinephrine concentration in association with a slight reduction in systolic blood pressure and a slight increase in heart rate, plasma cyclic adenosine monophosphate (cyclic AMP) concentration, and renin activity at 1 hr. All normal subjects complained of headache or felt heavy-headed after NTG administration. In the 13 patients with CHF, NTG significantly decreased plasma norepinephrine and cyclic AMP concentrations in association with a significant increase in the cardiac index and a significant reduction in pulmonary arterial diastolic pressure, systemic vascular resistance, systolic blood pressure, and heart rate. The effects occurred at 30 min after NTG administration and continued for 3 hr. Relief from dyspnea or orthopnea in patients with CHF was observed. NTG did not change the plasma cyclic GMP concentration in normal subjects and patients with CHF. We conclude that in patients with CHF, NTG decreases the enhanced sympathetic nervous activity, with concomitant beneficial effects on hemodynamics and improvement of clinical symptoms. In contrast, NTG increases sympathetic nervous activity in normal subjects.     

慢性心力衰竭患者血浆AVP、尿液水通道蛋白2的变化研究(附148例分析)

目的检测慢性心力衰竭(CHF)患者血浆精氨酸加压素(AVP)、尿液水通道蛋白-2(aquaporin-2,AQP2)水平,探讨血浆AVP、尿液AQP2与慢性心力衰竭及低钠血症的关系。方法应用双抗体夹心ELISA法检测148例慢性心力衰竭患者和68例健康对照者的尿液AQP2浓度,用放射免疫分析法同步检测血浆AVP,并测定血钠浓度。结果CHF患者血浆AVP、尿液AQP2的浓度比对照组明显增高(P<0.01),且心力衰竭越重、NYHY等级越高及血钠越低,血浆AVP、尿AQP2的浓度越高。结论AQP2是受血浆AVP调控的靶蛋白,尿液AQP2水平可以反映心力衰竭及低钠血症的严重程度。     

慢性充血性心力衰竭患者淋巴细胞β肾上腺素能受体密度与血小板钙含量相关性探讨

目的　研究慢性充血性心力衰竭（CHF）患者淋巴细胞β肾上腺素能受体（β-AR）密度是否与细胞内高钙负荷有关。方法　26例CHF患者及性别、年龄结构相似的正常健康人15名,取晨间清醒空腹状态下静脉血,用     

Carvedilol: a review of its use in chronic heart failure

Carvedilol (Dilatrend) blocks beta(1)-, beta(2)- and alpha(1)-adrenoceptors, and has antioxidant and antiproliferative effects. Carvedilol improved left ventricular ejection fraction (LVEF) in patients with chronic heart failure (CHF) in numerous studies. Moreover, significantly greater increases from baseline in LVEF were seen with carvedilol than with metoprolol in a double-blind, randomised study and in a meta-analysis. Carvedilol also reversed or attenuated left ventricular remodelling in patients with CHF and in those with left ventricular dysfunction after acute myocardial infarction (MI). Combined analysis of studies in the US Carvedilol Heart Failure Trials Program (patients had varying severities of CHF; n = 1094) revealed that mortality was significantly lower in carvedilol than in placebo recipients. In addition, the risk of hospitalisation for any cardiovascular cause was significantly lower with carvedilol than with placebo. Mortality was significantly lower with carvedilol than with metoprolol in patients with mild to severe CHF in the Carvedilol Or Metoprolol European Trial (COMET) [n = 3029]. The Carvedilol Prospective Randomised Cumulative Survival (COPERNICUS) trial (n = 2289) demonstrated that compared with placebo, carvedilol was associated with significant reductions in all-cause mortality and the combined endpoint of death or hospitalisation for any reason in severe CHF. All-cause mortality was reduced in patients who received carvedilol in addition to conventional therapy compared with those who received placebo plus conventional therapy in the Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN) trial (enrolling 1959 patients with left ventricular dysfunction following acute MI). Carvedilol was generally well tolerated in patients with CHF. Adverse events associated with the alpha- and beta-blocking effects of the drug occurred more commonly with carvedilol than with placebo, whereas placebo recipients were more likely to experience worsening heart failure. In conclusion, carvedilol blocks beta(1)-, beta(2)- and alpha(1)-adrenoceptors and has a unique pharmacological profile. It is thought that additional properties of carvedilol (e.g. antioxidant and antiproliferative effects) contribute to its beneficial effects in CHF. Carvedilol improves ventricular function and reduces mortality and morbidity in patients with mild to severe CHF, and should be considered a standard treatment option in this setting. Administering carvedilol in addition to conventional therapy reduces mortality and attenuates myocardial remodelling in patients with left ventricular dysfunction following acute MI. Moreover, mortality was significantly lower with carvedilol than with metoprolol in patients with mild to severe CHF, suggesting that carvedilol may be the preferred beta-blocker.     

纳洛酮对慢性心力衰竭患者血浆B型利钠肽水平及心功能的影响

目的观察纳洛酮对慢性心力衰竭（CHF）患者血浆B型利钠肽（BNP）水平及心功能的影响。方法 CHF患者102例随机分为纳洛酮组和对照组各51例,对照组采用常规治疗方法,纳洛酮组在对照组治疗基础上加用纳洛酮。治疗2周后比较2组血浆BNP水平及6min步行距离。结果 2组患者治疗后BNP水平低于治疗前,6min步行距离大于治疗前,差异均有统计学意义（P〈0.01）;且治疗后纳洛酮组BNP水平低于对照组,6min步行距离大于对照组,差异均有统计学意义（P〈0.05）。结论纳洛酮可改善CHF患者心功能,有效降低血浆BNP水平。     

重组人脑利钠肽和米力农治疗慢性心力衰竭急性发作期的对比研究

目的比较重组人脑利钠肽(rhBNP)和米力农治疗慢性充血性心力衰竭(CHF)急性发作期的临床疗效,观察rhBNP对心功能及血清脑利钠肽(BNP)和去甲肾上腺素(NE)水平的影响。方法入选CHF急性加重期患者100例,随机分为rhBNP组、米力农组各50例,观察2组治疗前后的临床疗效、心功能、血清BNP及NE水平变化。结果治疗后48h比较rhBNP组显效率及总有效率均高于米力农组(P<0.05),rhBNP组血清BNP、NE水平较米力农组下降(P<0.05),2组治疗后48h血清BNP、NE均较基线值下降(P<0.01);rhBNP组治疗后2周左室耐酚玫(LVEF)值较治疗前升高(P<0.05),米力农组治疗后2周EF值与治疗前比较差异无统计学意义(P>0.05)。结论 rhBNP能改善心室的收缩功能,延缓心室重构,可用于CHF急性加重期的治疗。     

普伐他汀短期治疗对慢性心衰患者心功能的影响

目的：探讨短期应用他汀类降脂药普伐他汀对慢性心衰患者心功能的作用。方法：64例慢性心力衰竭患者，随机分为普伐他汀治疗组(34例)和对照组(30例)，对照组给予强心、利尿、扩血管治疗，治疗组在此基础上加用普伐他汀，剂量为20mg，每晚1次，疗程8周，测定左室射血分数、血清肿瘤坏死因子-α和白介素-6及其变化。结果：普伐他汀治疗组与对照组比较，血清胆固醇有适度的下降；治疗后两组左室射血分数均有所提高，但普伐他汀组明显，与对照组比较，有统计学差异；治疗后与治疗前比较，普伐他汀组血清肿瘤坏死因子和白介素-6的降低比对照组更明显。结论：短期普伐他汀治疗能改善慢性心衰患者心功能和神经激素的平衡失调状况。     

米力农对充血性心力衰竭患者BNP的影响

目的 观察米力农治疗重症充血性心力衰竭（CHF）的临床疗效及其对脑钠素（BNP）的影响。方法 82例重症充血性心力衰竭患者,随机分为米力农组（42例）和对照组（40例）,对照组予以常规治疗,米力农组在常规治疗基础上静脉应用米力农7d,用放射免疫法测定血浆BNP在治疗前后的改变。结果 治疗后米力农组BNP水平明显降低,并明显低于对照组（P〈0．01）。心功能改善1～2级,药物副反应少,患者耐受性好。结论 米力农治疗CHF疗效较好,并能在一定程度上改善心衰患者的神经内分泌失调。     

冠心病患者中无心功能不全与合并心功能不全的脂联素水平观察

目的血清脂联素（adiponectin,APN）,一种脂肪组织来源的胶原样血浆蛋白,具有抗动脉粥样硬化、抗炎及改善胰岛素敏感性等作用,本文旨在探讨冠心病无合并心功能不全组与冠心病合并心功能不全组血清脂联素水平及其与NTproBNP的关系,及探讨脂联素在冠心病合并慢性心功能不全发病机制中的作用。方法收集连续入院的冠心病合并NYHAⅡ-Ⅳ级患者60例和冠心病无心功能不全患者60例的血清和临床资料,选取性别与年龄与病例组相匹配对照组25例,测定空腹血清脂联素水平、N末端前脑钠肽（N-terminal portion of proBNP,NTproBNP）、hsCRP（high sensitivity C-Reactive Protein）及生化指标,比较各组间脂联素水平及与NTproBNP、hsCRP及生化指标的关系。结果冠心病患者中无心功能不全组血清脂联素显著低于对照组,而冠心病合并心功能不全组显著高于冠心病无心功能不全组及对照组,且冠心病合并心功能不全组随着心功能不全分级的增加,脂联素水平是升高的。Spearson偏相关分析显示经年龄、性别及BMI校正后冠心病组脂联素水平与NT-proBNP、hs-CRP呈正相关,与LVEF、TC、TG呈负相关,多元逐步回归分析显示NTproBNP、HDL-C、TC是影响血浆APN的独立因素。结论本文研究发现冠心病无心功能不全患者血清脂联素水平明显低于对照组,而在冠心病合并心功能不全组血清脂联素是明显高于其他二组,且随着心功能不全分级的增加而明显递增,同时冠心病患者血清脂联素与NTproBNP及hsCRP呈正相关,提示脂联素可能参与冠心病及心功能不全的发病机制,其确凿的作用机制还有待进一步的深入研究证明,血清脂联素的变化趋势对于心功能不全的进展及转归可能有一定的指导意义。     

Pharmacodynamics and pharmacokinetics of nifedipine in patients with congestive heart failure

Twenty-seven cases of congestive heart failure (CHF) were treated with nifedipine (Nif) 20 mg po. Significant improvements in resting hemodynamics were found in 22 cases. The higher the basal systemic vascular resistance (SVR) and pulmonary artery end diastolic pressure (PAEDP) were, the greater the magnitudes of reduction found (r = 0.84 and 0.77, P less than 0.01, respectively). Exercise hemodynamic investigation showed that Nif led to a lowering of SVR, PAEDP and pulmonary vascular resistance (PVR), with increases in SV and concentration of 5-10 ng/ml, with a maximum being observed at the concentration of 20 ng/ml. No further vasodilation was found when the plasma concentration exceeded 20 ng/ml. No remarkable deviations from the normal ranges of Nif pharmacokinetics were found in CHF patients. The plasma norepinephrine level decreased markedly 2 and 7 h after Nif. Thus, it is concluded that oral Nif is beneficial in severe CHF patients having low cardiac output and high SVR.     

The pharmacists' role in improving guideline compliance for thyroid function testing in patients with heart failure

This single-center retrospective pilot program's objective was to utilize outpatient pharmacists to improve laboratory test adherence in chronic heart failure (CHF) patients overdue for thyroid function testing, thereby demonstrating the value of the outpatient pharmacist and justifying possible clinical role expansion. Thyroid disorders may contribute to CHF development, progression, and exacerbation. Testing is the standard of care in CHF patients per American Heart Association's 2009 Guidelines. Delinquency was defined as labs not conducted within 1 year in patients with euthyroid history, within 6 months in patients with thyroid dysfunction, abnormal labs at any time without follow-up, or lab absence after thyroid medication initiation, adjustment, or discontinuation. Targeted 80 nonpregnant adult CHF patients with delinquent thyroid function tests were counseled to get thyroid labs at point of sale, via telephone, e-mail, or letter. In collaboration with physicians, pharmacists ordered thyroid-stimulating hormone (TSH) and free T4 (FT4) labs. For patients with abnormal laboratory results, pharmacists coordinated drug therapy and follow-up labs. Data were collected from November 1, 2009 to March 30, 2010. Seventy-two patients (90%) previously delinquent for thyroid function testing received relevant thyroid labs. Ten patients (12.5%) with abnormal thyroid function tests not on prior drug therapy received treatment.     

Effects of V2-receptor antagonist tolvaptan and the loop diuretic furosemide in rats with heart failure

Diuretics are frequently required to treat fluid retention in patients with chronic heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohormonal activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V(2) receptor (V(2)R) and its levels are increased in CHF. This study was conducted to characterize the diuretic effect of tolvaptan, a non-peptide AVP V(2)R antagonist, and furosemide, a loop diuretic in a rat model of CHF after experimental autoimmune myocarditis. CHF was elicited in Lewis rats by immunization with porcine cardiac myosin, and 28 days after immunization rats were treated for 28 days with oral tolvaptan, and furosemide. CHF was characterized by left ventricular remodeling and impaired systolic and diastolic function. Tolvaptan produces a diuresis comparable to furosemide. Unlike tolvaptan, furosemide significantly increased urinary sodium and potassium excretion. Tolvaptan markedly elevated electrolyte-free water clearance (E-CH(2)O) or aquaresis to a positive value and increased urinary AVP excretion. In contrast to tolvaptan, furosemide elevated only electrolyte clearance (E-Cosm) but not E-CH(2)O. The differences in diuretic profile reflected the changes in plasma sodium and hormone levels. Tolvaptan dose dependently elevated plasma sodium concentration, but furosemide tended to decrease it. Furosemide significantly elevated plasma renin activity and aldosterone concentration. On the other hand, tolvaptan did not affect these parameters. Our results suggest that, tolvaptan have a potential medical benefit for the treatment of edematous conditions in CHF by removing excess water from the body without activating the RAAS or causing serum electrolyte imbalances.     

The enhanced plasma levels of soluble tumor necrosis factor receptors (sTNF-R1; sTNF-R2) and interleukin-10 (IL-10) in patients suffering from chronic heart failure are reversed in patients treated with beta-adrenoceptor antagonist

1 Cytokines may parallel or regulate the beneficial effects of beta-adrenoceptor antagonist treatment observed in chronic heart failure (CHF) patients. Therefore, this study was performed in order to investigate alterations of cytokine levels in beta-blocker-treated patients suffering from CHF. 2 We investigated plasma cytokine levels in eight healthy controls and 12 CHF patients. The patients were treated with standard medication (CHFstd) or with standard medication and additional beta1-blocker metoprolol (CHFmet). Interleukin-(IL)-1alpha, IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF), soluble TNF receptor type 1 (sTNF-R1), sTNF-R2, and sCD14 were measured by ELISA. 3 IL-1alpha and IL-1beta were not detectable in any of the tested groups. IL-2, TNF, or sCD14 were not altered as compared with healthy control subjects. CHFstd patients expressed enhanced IL-1ra, IL-6, IL-8, IL-10, sTNF-R1 and sTNF-R2. In CHFmet patients IL-1ra, IL-6 and IL-8 remained at the same level. In contrast, sTNF-R1 levels were significantly reduced, although not to control, whereas the sTNF-R2 and IL-10 were reduced to control levels. 4 The cAMP levels of mononuclear cells--recalculated for the patients included in this study from previous work [Werner et al. (2001). Basic Res. Cardiol., 96, 290]--correlated inversely with the sTNF-R2 data (Pearson, r = -0.46; P = 0.041; Spearman, r = -0.64, P = 0.002). 5 The present data indicate an interaction of the neurohumoral and the cytokine system in CHF patients at the cAMP level. Thus, measurement and correlation of sTNF-R2 and cAMP may provide a tool useful during investigation of beta-blocker therapy.     

慢性阻塞性肺疾病急性发作期的糖代谢改变

目的 :探讨慢性阻塞性肺疾病 (COPD)患者急性发作期的糖代谢改变。方法 :采用口服葡萄糖耐量试验 ,胰岛素释放试验检测26例COPD急性发作期患者血糖及胰岛素水平。结果 :中重度低氧血症患者空腹血糖及血浆胰岛素水平明显增高 ,胰岛素敏感指数明显下降 ,与轻度低氧血症患者相比差异有显著性 (P<0 001 ,P<0 05,P<0 001) ,血糖与PaO2 呈显著负相关(r= -0.5242,P<0 05) ;中重度低氧血症患者各时点血糖水平较轻度低氧血症患者显著性增高 (P<0 05) ;胰岛素释放试验两组差异无显著性。但两组胰岛素释放时间均明显延长。结论 :COPD急性发作期合并低氧血症患者存在糖耐量减低。     

血浆B型脑钠肽在急性呼吸道感染合并心力衰竭患者动态变化及对预后的影响

目的探讨B型脑钠肽（BNP）在急性呼吸道感染合并心力衰竭（CHF）患者中的变化及对预后的影响。方法选取262例急性呼吸道感染合并CHF患者（CHF组）,其中Ⅱ级68例,Ⅲ级92例,Ⅳ级102例;同期住院的老年急性呼吸道感染但无CHF的患者200例作为对照人群（非CHF组）,进行BNP检测及心脏左室射血分数（LVEF）、左室舒张末期内径（LVEDD）监测,对住院1个月后再次入院率及病死率进行分析。结果非CHF组患者BNP、LVEF、LVEDD分别为（526．12±11．18）pmol／L、（65．67±6．28）％、（37．76±5．59）mm,CHF组为（1522．03±42．27）pmol／L、（36．62±8．83）％、（52．89±5．22）mm,两组差异有统计学意义（P〈0．05）;CHFⅢ级与Ⅱ级、Ⅳ级与Ⅱ级在BNP、LVEF、LVEDD等指标差异有统计学意义（P〈0．05）;CHF患者出院时BNP〈400pmol／L183例为低浓度组,BNP≥400pmol／L79例为高浓度组,1个月后再次入院率低浓度组为6．57％（12／183）,高浓度组为39．24％（31／79）,高浓度组病死率5．06％,低浓度无死亡,再次人院率及病死率均差异有统计学意义（P〈O．05）。结论BNP的动态变化能较好的预测急性呼吸道感染合并CHF患者的预后。