β-受体阻滞剂治疗慢性心力衰竭研究进展

目前的研究结果表明，心脏重塑是心力衰竭（HF）发生、发展的基本机制。在初始的心肌损伤后，神经激素—细胞因子的长期、慢性激活促进心脏重塑，加重心肌损伤和心功能恶化犤１犦。交感神经系统激活在心脏重塑过程中起重要作用，多项以死亡率为主要观察终点的大规模临床试验证实，β－受体阻滞剂（以下简称：β－阻滞剂）治疗可显著减少HF病人的主要终点事件。目前β－阻滞剂已成为治疗慢性HF的重要药物之一。本文简要介绍β－阻滞剂治疗HF的一些新观点。１β－阻滞剂治疗HF的机制１．１HF时交感神经系统激活交感神经系统激活是HF最早…     

慢性心力衰竭与心肌生物能量代谢

慢性心力衰竭(CHF)是各种心脏疾患的终末状态.大量研究发现,正常心肌和心力衰竭(HF)心肌的能量代谢的特点有所不同,研究发现调节心肌能量代谢有望成为治疗心衰的一种新策略[1].本文对正常心肌的能量代谢,心衰时能量代谢的变化、能量调节,心衰的评估以及临床应用的相关进展做一综述.     

心力衰竭的药物治疗

心力衰竭的临床后果,部分是由于加重心脏负担的继发性生理学变化所造成的。上述许多生理紊乱能用药物控制,从而提高心输出量,往往会获得满意的症状改善。由以下主要原因所引起的心力衰竭如甲亢、贫血或房颤,是可针对病因治疗的。药物治疗基础心力衰竭可通过控制液体潴留和改善心输出量来处理。泵功能的力学改善可以由降低心脏工作负荷而获得,包括控制心室肌在     

基于代谢组学和网络药理学方法探讨芪参益气滴丸改善心衰大鼠心脏能量代谢的作用机制

组学与生物信息学为中药机制研究带来了新的思路。本研究采用代谢组学和网络药理学联合策略探讨芪参益气滴丸(Qishen Yiqi dropping pill, QDP)改善心力衰竭(heart failure, HF)大鼠心脏能量代谢的药效物质基础及网络调控机制。1H NMR代谢组学分析从HF大鼠心脏组织中发现肉碱、谷氨酰胺、肌酸、脯氨酸、高瓜氨酸、乳酸、牛磺酸和丙氨酸等8个代谢物在QDP治疗后显著回调,表明QDP调控糖、脂、ATP和蛋白质代谢等过程。动物实验操作均遵循中国医学科学院药物研究所实验动物管理与动物福利伦理委员会的规定。利用网络药理学建立“药物-成分-靶点-疾病”网络,并结合代谢组学结果提取与上述代谢过程相关的“成分-靶点”子网络,显示了QDP调节能量代谢潜在的47个作用靶点和79个化学成分,提炼了熊果酸、三七皂苷、人参皂苷等关键化学成分与INS、PPARG、AKT1等核心靶点,同时也从能量代谢的角度展示了QDP与HF之间多靶点、多成分的复杂作用关系。分子对接技术验证了部分靶点与化学成分良好的相互作用,其结合能均小于-5 kcal·mol^-1。本研究结果为...     

如何优化心力衰竭合并感染患者的抗菌药物治疗策略

心力衰竭(HF)是指心肌收缩功能或舒张功能下降,心脏负荷、外周血管阻力增加、心排出量急剧下降的心脏疾病,起病急、病情进展迅速[1-2]。感染是引发HF的常见诱因,同时HF患者合并感染和死亡的风险高。由于HF患者血流动力学变化可导致抗菌药物药代动力学/药效学(PK/PD)参数的变化,因此,该类患者需进行个体化抗感染治疗。     

半乳糖凝集素-3在心力衰竭临床应用中的研究进展

心力衰竭(HF）是心血管疾病发展到中晚期的一组复杂临床综合征,高发病率和病死率使其成为巨大的公共卫生负担。半乳糖凝集素-3(Gal-3)是近年来出现的新型生物标志物,大量研究证实其与HF的发生、发展密切相关,在HF患者临床管理应用中的价值日益突出。Gal-3参与心肌的纤维化和炎症反应,能直接反映心脏纤维化和心室重构的进程。Gal-3血清含量升高可促进心肌纤维化,降低心功能,增加HF患者的全因病死及再住院风险,因此监测该指标有助于HF的诊断及指导治疗,对HF患者的预后评估有着重要的临床意义。本文主要综述了Gal-3的结构、功能,Gal-3在HF临床诊断、预后评估中的作用,以及通过抑制Gal-3表达及中医药干预来辅助治疗HF。     

心力衰竭治疗新靶点-Galectins．3

尽管心力衰竭（HF）的药物治疗近年来有了较大进展,但HF患者预后仍很差。针对HF发病早期行药物治疗是近年来研究的一个重点。Galectin．3（Gal-3）在心室重塑和HF病理生理发展过程中起重要作用,可作为HF治疗的靶点。Gal-3水平升高的HF患者可从醛固酮拮抗剂治疗中获益。本文简要综述以Gal-3水平为指导的HF患者个体化治疗。     

抗心衰天然药物及活性化合物研究进展

心力衰竭(heart failure, HF)是世界性公众健康问题,全球心衰患者高达数千万人。其发病率每年递增,死亡率近年急剧上升,且有年轻化趋势,尽管近年来医学发展迅猛,但心衰的不良预后至今未得到有效改善。天然药物及其活性化合物具有温和低毒、多靶点综合疗效等特点,在恢复心脏功能、减轻能量障碍和提高生活质量等方面均具有明显优势。近年来在临床抗心衰应用中日益广泛,对天然药物及其活性化合物抗心衰机制进行深入研究,将为抗心力衰竭的临床治疗提供新的研究靶点和治疗方法。     

新型强心药的作用机制

充血性心力衰竭的治疗焦点是通过调控心脏的信号传导控制心肌重构,因此通过强心药物改善心脏的收缩功能是一种非常重要的治疗手段,本文主要综述了最新开发的强心药物及其临床疗效。     

TGF-β/Smads信号通路在心力衰竭心肌纤维化中的作用及中医药干预研究现状

在心力衰竭(HF)进展过程中,转化生长因子-β(TGF-β)/Smads信号通路的异常转导是HF心肌纤维化(MF)的重要机制。TGF-β是MF的关键因子,在HF MF过程中处于过度表达状态。Smads是TGF-β下游的主要效应因子,TGF-β/Smads通路诱导肌成纤维细胞异常增殖,加重心肌细胞外基质沉积,使心脏组织抗纤维化能力减弱,在HF MF的发病机制中发挥复杂作用。中医药在防治HF MF方面具有明确抑制心肌胶原沉积、抗心肌纤维化、保护心肌和改善心脏功能等功效。TGF-β/Smads通路是中药单体、中药复方、中成药发挥HF心肌保护作用的关键通路之一。本文对近10年来中医药干预TGF-β/Smads通路治疗HF MF现有的实验研究成果进行综述,以期为HF MF的防治及新药开发提供理论依据。     

Energy metabolism disorders and potential therapeutic drugs in heart failure

Heart failure (HF) is a global public health problem with high morbidity and mortality. A large number of studies have shown that HF is caused by severe energy metabolism disorders, which result in an insufficient heart energy supply. This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure, which determine the development of HF and recovery of heart. Current HF therapy acts by reducing heart rate and cardiac preload and afterload, treating the HF symptomatically or delaying development of the disease. Drugs aimed at cardiac energy metabolism have not yet been developed. In this review, we outline the main characteristics of cardiac energy metabolism in healthy hearts, changes in metabolism during HF, and related pathways and targets of energy metabolism. Finally, we discuss drugs that improve cardiac function via energy metabolism to provide new research ideas for the development and application of drugs for treating HF.KEY WORDS: Heart failure, Energy deficit, Cardiac dysfunction, Energy metabolism, Substrate metabolism, Hormones, Natural products, Synthetic drugs     

左卡尼汀对糖尿病心力衰竭患者的治疗作用

目的探讨左卡尼汀对糖尿病心力衰竭患者的治疗效果及其对血糖、血脂的影响。方法将90例糖尿病心功能不全患者随机分为两组:对照组44例给予常规治疗,左卡尼汀组46例在常规治疗基础上加用左卡尼汀2.0g1次/d静脉滴注。治疗3周后比较两组心功能及血糖、血脂变化。结果左卡尼汀组治疗后射血分数明显高于对照组(36.7±3.6vs31.7±4.2,P<0.05),左室舒张末期内径、左室收缩末期内径明显小于对照组(40.6±1.6vs44.9±2.7、56.2±4.0vs61.3±2.9,P<0.05),且空腹血糖也较对照组明显降低(6.05±2.13vs7.14±3.16,P<0.05)。结论左卡尼治疗糖尿病心力衰竭不仅能改善患者心功能,提高运动耐力,而且还可降低血糖,并能调节血脂。     

曲美他嗪对冠心病慢性心力衰竭的疗效观察

目的观察曲美他嗪对冠心病慢性心力衰竭的治疗效果。方法观察冠心病慢性心力衰竭患者62例,随机分为对照组和治疗组,其中对照组30例,应用血管紧张素转换酶抑制剂、硝酸酯类、钙拮抗剂、13受体阻滞剂、地高辛、阿司匹林、氢氯噻嗪或呋塞米等进行常规治疗;治疗组32例,在上述常规治疗基础上加用曲美他嗪治疗,分别观察用药前及用药6月后两组患者临床心功能改善情况并测定超声心动图心功能指标LVEDD、LVESD、LVEF以及6min步行距离。结果用药6月后曲美他嗪组患者的总有效率明显优于对照组,LVEDD、LVESD及LVEF均显著改善,6min步行距离明显延长,与对照组比较差异有统计学意义（P〈0．05）。结论曲美他嗪通过改善缺血心肌细胞的能量代谢,可显著改善冠心病慢性心力衰竭患者的临床心功能分级和心脏收缩功能,治疗效果确切。     

Modulation of fatty acids oxidation in heart failure by selective pharmacological inhibition of 3-ketoacyl coenzyme-A thiolase

A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the heart. Pharmacological agents that directly inhibit fatty acid oxidation include inhibitors of 3-ketoacyl coenzyme A thiolase (3-KAT), the last enzyme involved in ss-oxidation. The most extensively investigated agents of this group of drugs are trimetazidine and ranolazine. Clinical studies have shown that these agents can substantially increase the ischemic threshold in patients with effort angina. However, the results of current research is also supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism by 3-KAT inhibitors could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial effects of this new class of drugs on left ventricular dysfunction and glucose metabolism is reviewed and discussed.     

Acute phase protein orosomucoid protects against heart failure through CCR5-mediated improvement in energy metabolism and calcium sensitivity

OBJECTIVE Improving energy metabolism is a promising target for the treatment of heart failure(HF). Our previous studies found that acute-phase protein ORM could increase glycogen content and muscle endurance in skeletal muscle via CCR5-AMPK pathway. Here,we further explored the effect and mechanism of ORM in HF. METHODS HF mice were induced by left anterior descending(LAD) coronary artery ligation(MI). ORM1 knockout mice were generated by our lab previously,ORM overexpression lentivirus(ov-ORM) was injected into the infarcted myocardium to overexpress ORM. Heart function was detected by echocardiography and hemodynamic parameters were measured by AD Instruments Power Lab data acquisition and analysis system. ORM expression was detected by Western blotting and ELISA.Cardiomyocytes were generated from human induced pluripotent stem cells(i PSC). iPSC cardiomyocyte contraction and viability were examined by Cardio Excyte-96. We used the whole cell voltage-clamp technique to record L-type Ca~(2+)currents. The specific binding of ORM to CCR5 was examined by confocal microscopy. Glycogen,ATP and ATPase activity were detected by corresponding assay kit. We used a Seahorse XF96 Extracellular Flux Analyzer to measure oxygen consumption rate of i PSCCMs. We performed Ion Optixto assess cytosolic Ca~(2+) transient and myofilament sensitivity to Ca~(2+). RESULTS ORM expression in serum, myocardial and liver tissues was significantly elevated in HF mice induced by left anterior descending(LAD) coronary artery ligation(MI).Exogenous and endogenous ORM could significantly improve cardiac function, while ORM knockout showed opposite effect and shortened survival rate. In human induced pluripotent stem cel-derived cardiomyocytes(i PSCCMs), ORM treatment could promote its contraction without affecting beat rate, cell index and intracellular calcium.ORM was found to specifically bind to CCR5 in iPSCCMs. Blocking CCR5 with antagonist Maraviroc abolished ORM's effect in cardiac function and energy metabolism. Further studies found ORM increased calcium sensitivity, which was also blocked by CCR5 antagonist.CONCLUSION ORM might act as a novel endogenous inotropic protein. It could improve cardiac energy metabolism and increase calcium sensitivity via CCR5, indicating a potential therapeutic target for HF.     

Current pharmacotherapeutic strategies for cardiac arrhythmias in heart failure

ABSTRACT

Introduction: Heart failure (HF) affects over 6 million Americans and is the most common cause of hospital readmissions in the United States. Cardiac arrhythmias are common comorbidities seen in patients with HF and are associated with an increase in morbidity and mortality. Pharmacotherapeutic agents along with device and ablation therapies are the mainstays of treatment for cardiac arrhythmias in HF.

Areas covered: An extensive literature review of articles and clinical trials on PUBMED on the topic of pharmacotherapy for cardiac arrhythmias in heart failure was conducted. This review article summarizes the above literature to describe the prevalence of the various types of arrhythmias in HF, the recommended pharmacotherapies for the treatment of these arrhythmias in HF and the evidence that supports these recommendations.

Expert opinion: Cardiac arrhythmias are common in HF and are the leading cause of death in this patient population. The management of cardiac arrhythmias in HF is challenging. Pharmacotherapy is the primary though increasingly adjunctive therapy for most cardiac arrhythmias. Further, antiarrhythmic drugs must be used with caution in this patient population due to their potential adverse effects.     

Potential new drug treatments for congestive heart failure

Introduction: The prevalence of heart failure (HF) has increased globally in recent decades. Advances in our understanding of underlying pathophysiologic mechanisms have given rise to new therapies for treating the growing HF population. Nonetheless, morbidity and mortality associated with HF and its financial implications are daunting. Thus, novel therapies that can improve the natural history of HF patients are urgently needed.

Areas covered: This article reviews new investigational drugs being developed for the treatment of both acute decompensated heart failure (ADHF) and chronic heart failure with reduced ejection fraction (HFrEF). It presents the background of these drugs with a focus on their mechanism of action, their pharmacology, evidence from clinical studies and their potential role in HF management.

Expert opinion: The mortality benefit associated with serelaxin treatment in the RELAX-HF trial is being tested in RELAX-AHF II, while two other drugs, ularitide and TRV027, are also being evaluated in ADHF patients. Two new agents for the treatment of chronic HFrEF, LCZ696 and ivabradine, have been recently been approved for use by the FDA and four novel agents which have shown considerable promise in early studies, omecamtiv mecarbil, vericiguat, finerenone, and neuregulin, are currently being evaluated in late-phase clinical trials.     

降糖药物对糖尿病合并心衰患者的影响

糖尿病（DM）合并心力衰竭（HF）患者在临床上治疗和生存状态较差,而不同的降糖药物导致HF的风险不同。本文综述总结了目前各类降糖药物临床实验中对HF的影响：二甲双胍是一种相对安全的降糖药物;钠-葡萄糖共转运体-2（SGLT-2）抑制剂类降糖药可以降低危重心血管病和HF的风险,未来有望用于一线治疗,以改善HF患者的预后。     

厄贝沙坦对心力衰竭患者24小时心率变异性的影响

目的探讨心力衰竭患者24 h心率变异性(HRV)的变化及厄贝沙坦对心脏自主神经系统功能的影响。方法130例不同程度的心力衰竭患者随机分为2组,厄贝沙坦试验组(68例)和对照治疗组(62例),分别测定治疗前后24 h的心率变异性。结果心力衰竭患者心率变异性各时段没有区别(P>0.05),说明HF患者HRV昼夜节律消失。而厄贝沙坦能显著提高心力衰竭患者的24 h心率变异性,恢复昼夜节律性(P<0.05)。结论HRV可作为预测心力衰竭患者的病情和预后的监测指标,而厄贝沙坦对心力衰竭患者的心脏自主神经系统功能产生有益的影响。     

Rationale,design and organisation of an efficacy and safety study of oxypurinol added to standard therapy in patients with NYHA class III – IV congestive heart failure

Oxypurinol, the active metabolite of allopurinol and a potent xanthine oxidase inhibitor (XOI), is under evaluation as a novel agent for the treatment of congestive heart failure (HF). Several lines of evidence provide the rationale for the hypothesis that XOIs will improve clinical outcomes in patients with HF. First, XOIs have unique positive inotropic effects, improving myocardial contraction and performance while simultaneously improving myocardial energy metabolism. Second, XOIs ameliorate endothelial dysfunction in humans with HF. Finally, XO activity is upregulated in the heart and vasculature of subjects with HF, which may in turn contribute to oxidative stress and/or increased uric acid levels. Together these findings form the rationale for the Controlled Efficacy and Safety Study of Oxypurinol Added to Standard Therapy in Patients with New York Heart Association (NYHA) class III – IV Congestive Heart Failure (OPT-CHF) trial (Food and Drug Adminstration IND 65,125), a Phase II – III prospective, randomised, double-blind, placebo-controlled trial, which will include patients with stable symptomatic HF in NYHA class III – IV congestive HF who are deemed clinically stable on a standard and appropriately maximised heart failure therapy regimen. The efficacy end point for OPT-CHF is a composite that incorporates measures of patient outcome and well-being.