充血性心力衰竭炎性细胞因子的改变

目的 :探讨充血性心力衰竭 (CHF)时肿瘤坏死因子 α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 1β(IL 1β)和一氧化氮 (NO)的变化 ,及其与CHF关系。 方法 :CHF患者 4 5例和年龄匹配的对照者 17例 ,根据NY HA分级将CHF患者分成Ⅱ、Ⅲ、Ⅳ级 3组 ;根据体重分成恶病质组及非恶病质组。用酶联免疫法测定IL 6 ,用放射免疫法测定IL 1β、TNF α ,用比色法测定NO。 结果 :CHF组血清IL 6、IL 1β、TNF α和NO较对照组明显升高 ,IL 6、NO在心功能Ⅱ、Ⅲ、Ⅳ级时均显著升高 ,TNF α在Ⅲ、Ⅳ级时显著升高 ,而IL 1β在Ⅳ级时才显著升高。不同病因的CHF之间差异无统计学意义 ,恶病质组及非恶病质组之间差异也无统计学意义。血清TNF α与IL 6呈正相关 (r =0 .5 82 9,P <0 .0 1)。结论 :血清IL 6、IL 1β、TNF α、NO水平与CHF的严重程度密切相关 ,可作为判断CHF严重程度的指标 ;IL 6、IL 1β、TNF α在CHF的发生发展中可能起重要作用     

Pharmacotherapy in congestive heart failure: Vasopeptidase inhibition and its role in congestive heart failure

Vasopeptidase inhibition--that is, the dual inhibition of ACE and neutral endopeptidase-reduces blood pressure in a potent manner. Preliminary studies suggest that vasopeptidase inhibition can also effectively treat congestive heart failure. Additional corroborating studies to support the use of vasopeptidase inhibition in heart failure are now underway. (c)2000 by CHF, Inc.     

心力衰竭患者炎性与抗炎性细胞因子表达的平衡失调

目的 :了解炎性与抗炎性细胞因子在充血性心力衰竭 (CHF)过程中的变化及其临床意义。方法 :用双抗体夹心ELISA法测定 12 2例CHF患者及 30例健康人血浆中肿瘤坏死因子 α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 10 (IL 10 )的浓度。结果 :①CHF患者血浆中TNF α水平明显高于对照者 (P <0 .0 5或 <0 .0 1) ,且随着心力衰竭程度的加重 ,TNF α水平呈进行性增高 ;CHF患者血浆IL 6及IL 10水平 ,心功能Ⅲ、Ⅳ级者明显高于对照者 (P <0 .0 5或 <0 .0 1) ,而心功能Ⅱ级者与对照者相比差异无显著性意义。②TNF α与IL 6 (r =0 .6 18,P <0 .0 1)、IL 10 (r =0 .5 6 6 ,P <0 .0 1)均呈正相关 ,但TNF α与IL 10的比率 (TNF α/IL 10 )也随着心功能的恶化而升高 ,IL 10的升高与TNF α的升高相比明显不足。结论 :细胞因子的变化与心力衰竭的严重程度密切相关 ,CHF患者血中炎性细胞因子明显升高的同时伴有抗炎性细胞因子升高的相对不足 ,炎性与抗炎性细胞因子之间的平衡失调可能参与了CHF的发生发展     

心力衰竭患者部分神经激素和细胞因子的变化及卡维地洛的干预作用

目的:探讨充血性心力衰竭(CHF)患者部分神经激素、细胞因子的变化及与心功能的关系,观察卡维地洛对神经激素、细胞因子及心功能的影响,并比较不同剂量卡维地洛疗效的差别。方法:选择CHF患者90例,随机分成A、B、C3组。A组为对照组:予以血管扩张剂、利尿剂、地高辛等常规心力衰竭治疗。B组、C组在上述治疗基础上均予以卡维地洛口服,目标剂量B组:10mg,bid,C组:20mg,bid,然后维持稳定剂量至3个月。用药前后分别观察NYHA分级,左室射血分数(LVEF)、每搏量(SV)、短轴缩短率(FS)及醛固酮(ALD)、内皮素(ET)、肿瘤坏死因子(TNFα)、心钠素(ANP)等指标变化情况。结果:CHF患者心功能越差,神经激素、细胞因子水平越高。C组3个月后ALD、ET、TNFα、ANP水平与治疗前比较显著下降,LVEF、FS、SV明显提高,NYHA分级得到改善。B组除ET、TNFα、ANP有显著下降,LVEF明显升高外,其他指标改善不显著。A组上述指标与治疗前比较虽有改善,却差异无统计学意义。结论:①CHF患者神经激素和细胞因子水平明显升高,且与心功能分级及病情严重程度呈正相关;②卡维地洛可显著降低神经激素的激活及细胞因子的浓度,改善CHF患者心脏功能,其疗效呈剂量依赖性。     

Inflammatory heart disease: a role for cytokines

Inflammatory heart disease is a rising concern worldwide. Similar mechanisms link autoimmune diseases, including the association of increased disease with proinflammatory cytokines and the importance of regulatory mechanisms in the control of chronic inflammation. Many pathogens including bacteria, protozoa and viruses have been associated with heart disease in patients, and are able to induce similar disease in animal models. Recognition of pathogens by the innate immune system leads to release of proinflammatory cytokines that both reduce infection and increase chronic inflammatory heart disease. Elevated levels of proinflammatory cytokines are able to overcome tolerance to chronic disease, indicating that environmental factors are important in determining progression to chronic heart disease. Understanding the mechanisms leading to chronic heart disease will be critical for developing effective therapies to reduce cardiac dysfunction and heart failure.     

老年慢性心力衰竭患者细胞因子和心率变异性的相关性研究

目的 观察老年慢性心力衰竭(CHF)患者炎性细胞因子和心率变异性(HRV)的相关性.方法 128例60岁及以上老年CHF患者(CHF组),对照组50例为健康体检者.比较两组炎性细胞因子包括肿瘤坏死因子可溶性受体Ⅰ、Ⅱ(sTNF-RⅠ、sTNF-RⅡ)和白细胞介素6(IL-6)表达水平,24 h内的全部HRV参数[正常心动周期的标准差(SDNN)、24 h内5 min节段平均心动周期的标准差(SDANN)、24 h内全部5 min节段所有心动周期标准差的平均值(SDNNI)、相邻正常心动周期差值均方的平均根(rMSSD)和相邻两正常心动周期差值大于50 ms的个数所占的百分比(pNN50)],分析二者相关性.结果 CHF组患者HRV参数低于对照组:SDNN分别为(99.8±22.4)和(146.6±43.2)ms、SDANN分别为(85.5±23.6)和(138.7±40.9)ms、SDNNI分别为(41.7±15.8)和(56.9±18.8)ms、rMSSD分别为(23.4±13.0)和(30.0±12.9)ms、pNN50分别为(5.5±3.8)和(12.0±4.7)%;CHF患者炎性细胞因子明显高于对照组(均为P＜0.05);CHF患者HRV参数与炎性细胞因子浓度间呈负相关(r≥-0.44,P＜0.05).结论 炎性细胞因子sTNF-R Ⅰ、sTNF-RⅡ和IL-6可能是老年CHF患者HRV下降的原因之一.     

Chrome congestive heart failure: Activation and destruction of platelets in patients with rheumatic heart disease

We evaluated the activation and destruction of platelets in24 patients with rheumatic heart disease (RHD) involving themitral valve. Ex vivo platelet aggregation induced by adenosinediphosphate (ADP) and collagen was significantly increased inRHD patients as compared with normal controls. Plasma levelsof ß-thromboglobulin (ß-TG) and plateletfactor 4 were also elevated Plasma concentrations of glycocalicin,a proteolytic fragment of platelet membrane glycoprotein Ib.were increased, while platelet counts were decreased in RHDpatients as compared with normal controls. RHD patients with,versus those without, atrial fibrillation demonstrated significantdifferences in ß-TG levels and platelet counts. However,we observed no difference in glycocalicin levels between thetwo groups. The present study demonstrated that increased plateletactivation, as well as platelet destruction, occur in patientswith RHD.     

心力衰竭患者血浆细胞因子的变化及其临床意义

目的　探讨充血性心力衰竭 (心衰 ,CHF)患者血中肿瘤坏死因子 α(TNF α)和白细胞介素 6(IL 6)的变化及其临床意义。方法　双抗体夹心ELISA法测定 12 2例CHF患者及 3 0例健康人血浆中TNF α和IL 6的浓度。超声心动图测量左心室射血分数及左心室舒张末期内径 ,X线胸片测心胸比。结果　CHF患者血浆中TNF α水平明显高于对照组 (P <0 .0 5 ) ,且随着心衰程度的加重 ,TNF α水平呈进行性增高 ;IL 6水平仅在心功能Ⅲ级、Ⅳ级组中明显高于对照组 (P <0 .0 5 )。TNF α、IL 6与左心室射血分数呈负相关 (r =-0 .5 13 ,r =-0 .45 3 ,P <0 .0 1) ,与心胸比呈正相关 (r =0 .5 0 1,r =0 .43 8,P <0 .0 1) ;与左心室舒张末期内径呈正相关 (r =0 .3 42 ,r =0 .3 0 4,P<0 .0 1)。结论　CHF患者TNF α和IL 6升高可能是心功能恶化的免疫学标志之一 ,提示炎症机制参与心力衰竭的进程     

Proinflammatory cytokines, soluble Fas receptor, nitric oxide and angiotensin converting enzyme in congestive heart failure

We measured serum interleukin-2 receptor (sIL-2R), tumor necrosis factor-a (TNF-a), Fas receptor (sFas), nitric oxide (NO), and angiotensin converting enzyme (ACE) activity in 45 patients with congestive heart failure (CHF) of different etiologies. The relatioship between these bioindices and the severity of heart failure was analysed. Patients were classified according to the etiology of heart failure into: 15 patients with rheumatic valvular heart disease (RHD), 17 with ischemic heart disease (IHD) and 13 with idiopathic dilated cardiomyopathy (DCM). Patients were further classified according to severity of CHF following the New York Heart Association classification (NYHA) into: NYHA class II (n= 7), NYHA class III (n=20) and NYHA class IV (n=18). Eighteen healthy subjects were included as controls. Serum sIL-2R, TNF-alpha and sFas levels were determined by ELISA while serum NO and ACE levels were measured by colorimetric methods. Doppler Echocardiography was performed for all participants. Levels of sIL-2R, TNF-alpha, sFas, NO, and ACE were significantly higher in CHF patients than controls. Levels of the bioindices varied according to the CHF etiology. TNF-a level was the only one that had significant differences among different subgroups (RHD, IHD and DCM). The levels of sIL-2R, TNF-alpha, NO and sFas in patients with NYHA class IV were significantly higher than class II or III. Moreover, sIL-2R, TNF-alpha and NO levels were significantly higher in patients with diastolic dysfunction than patients with normal diastolic function. A significant positive correlations were found between sFas and both TNF-alpha and sIL-2R and between TNF-alpha and both NO and diastolic function. In addition, significant positive correlations were found between TNF-alpha and sIL-2R in both IHD and RHD patients and between sIL-2R and both ACE in IHD patients and diastolic function in DCM patients. It is concluded that a relationship exists between immune system activation, apoptosis and renin- angiotensin system in CHF and this may play a significant role in the pathophysiology and prognosis of the disease.     

卡维地络对充血性心力衰竭患者促炎细胞因子的影响

目的：观察卡维地络对充血性心力衰竭（CHF）患者促炎细胞因子浓度的影响。方法：选择66例CHF患者，随机分为常规治疗组和卡维地络治疗组，32例健康体检者为正常对照组。用双抗体夹心ELISA法测定血浆肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）和IL-1β的浓度，分析其与CHF程度的关系。结果：（1）CHF患者三种细胞因子浓度均明显高于正常对照组（P〈0．05或〈0．01），CHF程度越重细胞因子浓度越高（P〈0．01）；（2）治疗后卡维地络组心功能分级左室收缩末内径较治疗前显著降低（P均〈0．05），左室短轴缩短率（LVFS）、每搏量（SV）、左室射血分数（LVEF）较治疗前显著升高（P〈0．05～〈0．01）；常规治疗组仅LVEF显著升高（P〈0．05）；治疗后卡维地络组LVEF、LVFS较常规治疗组显著升高（P〈0．05）；（3）治疗后卡维地络组三种细胞因子浓度显著降低（P〈0．01或〈0．05）；常规治疗组TNF—α、IL-6降低（P〈0．05），而IL-1β水平降低不显著。结论：CHF患者促炎细胞因子浓度升高，可作为判断心衰严重程度的指标。卡维地络能有效抑制促炎细胞因子的产生，改善心功能和心室重构。     

Hemodynamic and clinical evaluation of piroximone, a new inotrope-vasodilator agent, in severe congestive heart failure

To assess the potential utility of piroximone (MDL-19,205), an investigational inotrope-vasodilator agent, in severe heart failure, 15 patients with severe left ventricular failure refractory to conventional agents were enrolled in an acute hemodynamic study. After incremental intravenous dosing (mean total dose 1.8 +/- 0.4 mg/kg body weight), cardiac index increased (1.7 +/- 0.3 to 2.6 +/- 0.6 liters/min per m2; p less than 0.001) and left ventricular filling pressure decreased (25 +/- 7 to 19 +/- 7 mm Hg; p less than 0.001). Also decreasing significantly were right atrial pressure (13 +/- 6 to 7 +/- 5 mm Hg; p less than 0.005) and systemic vascular resistance (1,633 +/- 394 to 1,183 +/- 278 dynes.s.cm-5; p less than 0.001). Heart rate and mean arterial pressure did not change, whereas stroke work index increased significantly (13.3 +/- 4.3 to 21.6 +/- 7.3 g.m/m2; p less than 0.005). The increase in stroke work index with a concomitant decrease in left ventricular filling pressure indicates an improvement in systolic performance after treatment with piroximone. Similar responses were obtained after incremental doses of piroximone in oral solution. After oral doses of piroximone tablets, cardiac index also increased significantly (2.1 +/- 0.6 to 2.4 +/- 0.5 liters/min per m2; p less than 0.05), although this magnitude of increase was comparatively low. In a subgroup of 10 patients who underwent equilibrium gated radionuclide blood pool scintigraphy before and after intravenous piroximone, end-diastolic volume index tended to increase (106 +/- 42 to 132 +/- 60 ml/m2; p = 0.07), whereas left ventricular filling pressure decreased significantly (26 +/- 8 to 19 +/- 9 mm Hg; p less than 0.01).     

The role of endogenous dopamine in congestive heart failure

Although the effects of epinephrine and norepinephrine in congestive heart failure have been extensively studied, and exogenous dopamine, another of the catecholamines, has been widely used for the treatment of congestive heart failure, little attention has been paid to the physiological significance of endogenous dopamine in this condition. The present study was therefore designed to assess the physiological significance of endogenous dopamine in congestive heart failure. Nineteen patients with congestive heart failure caused by such conditions as acute myocardial infarction, valvular disease and dilated cardiomyopathy were examined before and after treatment with diuretics, digitalis and vasodilators. Electrolyte, creatinine and catecholamine concentrations in plasma and urine were analyzed. Urinary dopamine levels were increased in 13 out of 19 cases before treatment and returned to the normal range after treatment, falling from 2448 +/- 950.7 to 528.8 +/- 56.3 micrograms/day (normal level, less than 700 micrograms/day). Urinary dopamine excretion was markedly elevated within 24 hours after the onset of symptoms of heart failure, such as chest pain, palpitations and dyspnea. The relationship between urinary dopamine excretion and time after the onset of symptoms showed a strong statistical correlation (r = 0.55, p less than 0.001). Urinary dopamine excretion was also well correlated with plasma dopamine concentration, urinary norepinephrine excretion and venous pressure. From these results, it is concluded that endogenous dopamine seems to play an important role during the acute phase of congestive heart failure.     

培哚普利、福辛普利对心衰和炎性细胞因子影响的比较

目的:比较培跺普利、福辛普利对心力衰竭患者的生存质量和炎性细胞因子的影响。探讨两药治疗心力衰竭的疗效与安全性。方法:87例心衰患者随机分为培跺普利组、福辛普利组和对照组。治疗前、后测定血清肿瘤坏死因子α(TNFα)、白介素 6(IL-6)、白介素1β(IL-1β)、血肌酐(Cr)、尿素氮(BUN)、血钾(K~+)、每搏量(SV)、心输血量(CO)、左室射血分数(LVEF)。同时进行6分钟步行试验(6MWT)、明尼苏达心衰问卷评分(ML WHF),记录用药过程中的不良反应。结果:治疗4周后,两组患者IL-6水平显著下降(P<0.01),福辛普利组TNFα水平下降(P<0.05)。两组患者SV、CO、LVEF水平均上升(P<0.01);6MWT显著增加(P<0.001);ML WHF明显下降(P<0.001);BUN、SCr、K~+无统计学变化。结论:培哚普利和福辛普利都能有效治疗心衰,减少炎性细胞因子,改善生活质量。福辛普利在降低TNFα上更有优势。     

Circulating interleukin-6 family cytokines and their receptors in patients with congestive heart failure

gp130 is a common signal-transducing receptor subunit for the interleukin (IL)-6 cytokine family. Studies in genetically engineered animal models have demonstrated a critical role for the gp130-dependent cardiomyocyte survival pathway in the transition to heart failure. In the present study, we examined plasma levels of the IL-6 family of cytokines and the soluble form of their receptors in patients with congestive heart failure (CHF). Circulating levels of the IL-6 family of cytokines, soluble IL-6 receptor (sIL-6R), and soluble gp130 (sgp130) were examined in 48 patients with various degrees of CHF, including dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), and valvular cardiomyopathy (VCM). Circulating levels of IL-6, leukemia inhibitory factor (LIF), and sgp130 significantly increased in association with the severity of CHF. No significant difference was observed in the circulating levels of sIL-6R and IL-11 among these patients. Interestingly, DCM patients showed higher circulating sgp130 levels than patients with ICM or VCM. Our findings suggest that gp130 expression in the heart is likely to be dynamic, and that the IL-6 family of cytokines and their common receptor gp130 participates in the pathogenesis of CHF, especially in DCM.     

Refractory oedema in congestive heart failure: a contributory role of loop diuretics

Abstract. We report a patient with congestive heart failure (CHF) who presented with massive oedema resistant to therapy with maximal doses of loop diuretics, despite an adequate renal function. After a diuretic pause and dietary salt restriction, a conventional dose of furosemide in combination with distally active diuretics induced a prompt weight loss exceeding 30 kg with stable renal function. We suggest that the ‘refractory’ oedema in this patient was due to a combination of CHF and inappropriate (loop) diuretic therapy in conjunction with a high dietary sodium intake. We conclude that in the absence of hyponatraemia and renal failure, even severe oedema may not represent a negative prognostic indicator. The recognition of diuretic-associated mechanisms complicating cardiac oedema is essential to avoid the vicious circle of worsening oedema whilst escalating therapy with loop diuretics.     

The hemodynamic and clinical responses to terazosin, a new alpha blocking agent, in congestive heart failure

To determine the hemodynamic effects of a new alpha 1 blocker, terazosin, in congestive heart failure, six patients with this condition underwent hemodynamic testing (at rest and during exercise) before and after dosing. Doses of 2, 5, and 10 mg were examined in sequence over 3 days to define dose-response characteristics. Terazosin, in these doses, decreased pulmonary and systemic vascular resistances and right atrial and pulmonary capillary wedge pressures. Terazosin increased stroke volume and cardiac output, presumably through afterload-reduction, without altering heart rate. These aforementioned responses were apparent both at rest and during exercise. While a direct relationship existed between dose and plasma concentration, a similar relationship was not observed for dose (or plasma concentration) and hemodynamic response; no differences were noted between the hemodynamic responses to the three doses. Improvement in hemodynamics persisted and the clinical status and exercise capacity improved in the four patients chronically treated (over 2 months) with terazosin. Treating the heightened tone of the sympathetic nervous system in congestive heart failure with the alpha 1 blocker, terazosin, may be of benefit to some patients afflicted with this disorder.     

The role of angiotensin-converting enzyme polymorphism in congestive heart failure

Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase, with primary known functions of converting angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II and inactivating bradykinin. There is high variability among individuals in ACE concentrations, mainly due to the presence of a genetic polymorphism. The ACE gene has, in fact, insertion/deletion polymorphism in intron 16, consisting of a 287-base pair Alu repeat sequence, with three genotypes: insertion polymorphism, insertion/deletion polymorphism, and deletion polymorphism. The genetic effect accounts for 47% of the total variance of serum ACE. The determination of this polymorphism has allowed researchers to study the implications of the ACE gene in many case-control studies of cardiovascular disease, including myocardial infarction and hypertrophic and dilated cardiomyopathy. We review the current knowledge about the ACE gene polymorphism and its implications in heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Interpretation of the results of studies about the role of this polymorphism are controversial. The repetition of epidemio-genetic studies and the creation of adequate experimental studies will help to definitively establish the pathogenetic role of the permanent increase in ACE expression associated with the deletion polymorphism genotype.     

Treatment of congestive heart failure: new concepts

In the past, hemodynamic factors, in congestive heart failure were considered as being of major importance in the production of the major symptoms and signs of the disease: peripheral (increased oxygen extraction, flow redistribution) or central (Starling's law, myocardial contractility). More recently, excessive hormonal compensation has been felt to be more important such as: The renine-angiotensin-aldosterone axis, Circulating catecholamines, Arginin-vasopressin. These hormones are responsible for water and sodium retention, tachycardia and increase in peripheral resistance. Newer agents such as Captopril are effective in blocking the action of these endocrine factors.