肾素-血管紧张素系统阻断剂与心房颤动

心房颤动是临床最常见的心律失常之一,发病率呈增加趋势。心房电重构和结构重构是心房颤动维持和复发的主要机制,肾素-血管紧张素系统在心房重构中起重要作用。肾素-血管紧张素系统阻断剂（血管紧张素转化酶抑制剂和血管紧张素受体阻断剂）通过抑制心房不应期缩短和抗心房结构重构等作用抑制心房重构并减少心房颤动的发作。肾素-血管紧张素系统阻断剂影响心房结构和功能,为心房颤动的防治提供了一种新的选择。     

心房颤动患者心房纤维化研究进展

心房颤动的发生和维持与心房重构有关。心房纤维化是心房颤动患者心房结构重构最突出的表现,目前被认为是发生心房颤动的结构基础,是心房颤动发生、维持的一个重要因素。现综述心房颤动患者心房纤维化及其发生机制。通过对心房颤动患者心房纤维化结构改变及肾素-血管紧张素系统、转化生长因子、基质金属蛋白酶等在心房纤维化的发生和心房颤动发生、维持中的作用等的全面阐述,,探讨了心房颤动患者心房纤维化的研究进展。防治心房颤动新的策略取决于对心房纤维化机制更好的理解。     

肾素-血管紧张素-醛固酮系统在心房颤动患者心房重构中的研究进展

心房颤动是临床上最常见的心律失常之一,有较高的发病率和致残率,严重影响患者的生活质量。心房颤动的病理生理学改变主要表现为心房重构,越来越多证据表明肾素-血管紧张素-醛固酮系统激活在心房电重构和结构重构及最终导致心房颤动发生的过程中发挥重要作用。现综述肾素-血管紧张素-醛固酮系统参与心房结构重构的可能机制及临床抗心房重构的治疗现况,为进一步探讨心房颤动临床治疗提供新思路。     

心房颤动的病理生理和危害

一、心房颤动的病理生理改变 1.心房结构重构:电重构、收缩重构和结构重构被认为是心房颤动(简称房颤)的特点,而结构重构被认为是房颤维持的主要因素.研究显示,心房间质纤维化导致的心房传导障碍是房颤发生、维持的一个重要因素.在分子水平,房颤患者血管紧张素Ⅱ、转化生长因子-β1、炎症与氧化应激对细胞外基质失调和心房纤维化发挥着重要的作用.     

炎症反应与心房颤动的关系

心房颤动发病机制复杂,心房重构起着至关重要的作用,而心房重构又包括结构重构和电重构。心房重构的病理生理机制与炎症反应密切相关,二者的联系复杂多样,一些潜在的疾病以及内环境改变都可能影响到这些途径,从而导致心房颤动的发生。炎症标志物也与心房颤动的发生、维持、复发、心房颤动负荷以及血栓形成有关。在这种情况下,是否应该给予心房颤动患者具体的抗炎干预措施目前尚存在争议。现对近几年的炎症反应与心房颤动关系的相关研究进行简要概括,同时提出炎症标志物在心房颤动中的预测作用。此外,纳入心房颤动患者实施抗炎干预的部分研究现状。     

老年性心房颤动心房电重构与钙离子机制研究进展

心房颤动是一种十分常见的心律失常,随年龄增长发病率增加。在心房颤动的发生机制中,心房电重构起着重要作用。本文就心房电重构的离子分子基础、钙离子机制在心房电重构发生和维持中的作用以及老龄对心房电重构影响的现阶段研究进展予以综述。     

心房颤动致心房重构分子机制研究进展

心房颤动是临床上一种常见的心律失常,心房颤动致心房重构是近年来研究发现的一个重要的电生理现象。心房颤动本身能够导致心房电生理、功能和结构的改变。本文综述了心房颤动致心房快速的电生理变化和缓慢的蛋白质表达及其分子改变机制。通过对心房电生理重构、离子重构和蛋白质重构和超微结构及其功能变化等不同方面的全面阐述,探讨了心房重构的分子机制研究进展。防治心房颤动新的策略将取决于心房重构机制更好的理解。     

氧化应激与心房颤动时的心房结构重构

心房颤动(简称房颤)具有自身进展性,主要由于房颤时心房发生电、结构和功能重构,而心房结构重构又在促进房颤发作并持续中发挥更重要作用。最新研究证实,房颤时心房肌的氧化应激产物增加、氧化还原基因表达失衡以及线粒体DNA存在氧化损伤,表明了房颤时心房肌存在氧化应激。氧化应激可能在房颤时心房结构重构过程中发挥重要作用。新近研究提示,一些具抗氧化作用的药物可能通过防止心房重构,减少房颤发生。     

醛固酮受体拮抗剂治疗心房颤动的研究进展

心房颤动是临床上最常见的持续性心律失常,近年来研究表明心房重构是心房颤动发生和维持的中心环节,心房重构包括电重构和结构重构,然而心房重构确切的机制尚未完全明确。近年来的研究表明,醛固酮与心房重构有着密切的关系。文章综述了醛固酮影响心房重构的机制以及醛固酮受体拮抗剂治疗心房重构的研究。     

转化生长因子-β1对心房结构重构及细胞骨架蛋白的影响

心房颤动是临床上最常见的持续性心律失常。大量研究发现,心房颤动的发生发展与心房结构重构密切相关,而心房纤维化是最主要的结构重构改变。转化生长因子-β1是心房颤动纤维化重构中重要的致纤维化因子,不仅能引起细胞间质重构,还能影响心肌细胞骨架重塑及相关骨架蛋白表达异常。特别是使心脏特异性肌动蛋白交联蛋白α-actinin-2表达增加。细胞骨架蛋白参与了结构重构改变。现对转化生长因子-β1对心房结构重构及心房肌细胞骨架蛋白的影响进行综述。     

心率与心房颤动关系的研究进展

心房颤动（简称“房颤”）是临床上最常见的心律失常,其发病率随年龄增长而增加。心房重构是房颤的核心机制,包括电重构、结构重构及自主神经重构。自主神经功能障碍在房颤的发生、发展中起着重要的作用,而心率可以间接反映自主神经功能。心率与房颤发生的关系以及房颤射频消融术后心率变化与房颤复发关系复杂,且一直在研究中。     

MicroRNAs与心房颤动

心房颤动是临床上最常见的心律失常,其易感因素众多、发病机制主要为心房电重构和结构重构,但具体分子调控机制尚不明确。微小RNA（MicroRNAs）是一类长度为18-25个核苷酸的内源性非编码小RNA,可通过与靶基因mRNA 3’非翻译区的不完全互补结合,在转录后水平抑制靶基因的表达。近年来研究发现microRNAs在心房颤动的发生发展过程中起到了重要作用。房颤相关的microRNAs主要包括miR-1、miR-26和miR-101,miR-133,miR-328、miR-21、miR-30等,主要通过调控离子通道的表达影响心房电重构,或通过调控心肌纤维化及细胞外基质沉积参与心房结构重构。     

Mechanisms of atrial remodeling and clinical relevance

PURPOSE OF REVIEW: Atrial fibrillation usually occurs in the context of an atrial substrate produced by alterations in atrial tissue properties referred to as remodeling. Remodeling can result from cardiac disease, cardiac arrhythmias, or biologic processes such as senescence. Recent advances in understanding remodeling have allowed for insights into mechanisms underlying atrial fibrillation that have been transferred from experimental models to humans. This paper reviews recent progress in understanding atrial remodeling, as well as the consequent clinical insights into atrial fibrillation pathophysiology and treatment. RECENT FINDINGS: Two principal forms of remodeling have been described in animal models of atrial fibrillation: ionic remodeling, which affects cellular electrical properties, and structural remodeling, which alters atrial tissue architecture. Atrial tachycardias (particularly rapid tachyarrhythmias such as atrial flutter and atrial fibrillation) cause ionic remodeling, which decreases the atrial refractory period and promotes atrial reentry. Congestive heart failure produces atrial interstitial fibrosis, which promotes arrhythmogenesis by interfering with atrial conduction properties. Recent animal studies have provided insights into the pathways involved in remodeling, and have indicated the pathophysiological role of remodeling in specific contexts. In addition, work in animal models has provided information about pharmacological interventions that can prevent the development of remodeling. Clinical studies have shown that novel approaches to remodeling prevention identified in animal work have potential therapeutic value in man. SUMMARY: Understanding atrial remodeling has the potential to improve our appreciation of the pathophysiology of clinical atrial fibrillation and to allow for the development of useful new therapeutic approaches.     

Electrophysiologic remodeling and drug treatment of atrial fibrillation

Since 1995, a number of studies have established and detailed the mechanisms of electrical and structural atrial remodeling induced by atrial fibrillation. Atrial remodeling involves many cellular components, from ionic channels to connexins. The determination of these mechanisms may help to define a new therapeutic targets of atrial fibrillation, a frequent arrhythmia that remains difficult to treat. Atrial remodeling prevention may lead to limit the evolution of the arrhythmia (early recurrences after reduction, AF secondary to atrial tachycardia, permanent AF, decrease in atrial contractility, sinus dysfunction). Except amiodarone, the usual antiarrhythmic drugs have no effect on atrial remodeling. Calcium channel inhibitors prevent early remodeling but have no effect on prolonged remodeling. Digoxin increases remodeling. Angiotensin II receptor inhibitors have been shown to prevent early AF recurrence after reduction and are very promising in such a direction. Other methods such as the one of antioxidant therapy seem to be promising and could define soon a new antiarrhythmic therapeutic class, the antiremodeling drugs.     

Electrical and structural remodeling: role in the genesis and maintenance of atrial fibrillation

Atrial fibrillation (AF) and congestive heart failure (CHF) are 2 frequently encountered conditions in clinical practice. Both lead to changes in atrial function and structure, an array of processes known as atrial remodeling. This review provides an overview of ionic, electrical, contractile, neurohumoral, and structural atrial changes responsible for initiation and maintenance of AF. In the last decade, many studies have evaluated atrial remodeling due to AF or CHF. Both conditions often coexist, which makes it difficult to distinguish the contribution of each. Because of atrial stretch in the setting of hypertension or CHF, atrial remodeling frequently occurs long before AF arises. Alternatively, AF may lead to electrical remodeling, that is, shortening of refractoriness due to the high atrial rate itself. In many experimental AF or rapid atrial pacing studies, the ventricular rate was uncontrolled. In those studies, atrial stretch due to CHF may have interfered with the high atrial rate to produce a mixed type of electrical and structural remodeling. Other studies have dissected the individual role of AF or atrial tachycardia from the role CHF plays in atrial remodeling. Atrial fibrillation itself does not lead to structural remodeling, whereas this is frequently produced by hypertension or CHF, even in the absence of AF. Primary and secondary prevention programs should tailor treatment to the various types of remodeling.     

Atrial remodeling in atrial fibrillation and some related microRNAs

Atrial fibrillation is the most common sustained arrhythmia associated with substantial cardiovascular morbidity and mortality, with stroke being the most critical complication. The role of atrial remodeling has emerged as the new pathophysiological mechanism of atrial fibrillation. Electrical remodeling and structural remodeling will increase the probability of generating multiple atrial wavelets by enabling rapid atrial activation and dispersion of refractoriness. MicroRNAs (miRNAs) are small non-coding RNAs of 20-25 nucleotides in length that regulate expression of target genes through sequence-specific hybridization to the 3' untranslated region of messenger RNAs and either block translation or direct degradation of their target messenger RNA. They have also been implicated in a variety of pathological conditions, such as arrhythmogenesis and atrial fibrillation. Target genes of miRNAs have the potential to affect atrial fibrillation vulnerability.     

MicroRNA与心房颤动关系的研究进展

心房颤动是最常见的持续性心律失常,并有较高的发病率和死亡率。其流行率预计在未来几年会进一步增加。尽管在过去十年中出现了心房颤动病理生理学的新分子概念,但目前可用的治疗方法仍存在主要局限性,包括效果差和严重的副作用,如心室恶性心律失常等。心房电重构、结构重构和自主神经重构是心房颤动的发病基础,但驱动这种重构的确切机制仍不完全清楚。MicroRNA代表大量小非编码RNA的亚组,降解或抑制其靶m RNA的翻译,从而调节基因表达并在广泛的生物学过程中起重要作用。临床上,越来越多的证据表明micro RNA在心血管疾病的发生发展中发挥关键作用。     

犬快速心房起搏房颤模型肺静脉及心房组织心肌纤维化定量分析

目的：探讨持续性房颤时肺静脉及心房结构重构的变化,以期进一步阐明房颤的发病机制。方法：将18只健康杂种犬随机分为对照组（n=8）和房颤组（n=10）。房颤组犬以400次／分快速心房起搏制备房颤模型。10周后分别取两组犬的左上肺静脉（LSPV）、左房峡部（LAI）、右心耳（RAA）处心肌进行心肌纤维定量分析,并进行对照研究。结果：房颤组各部位Ⅲ型胶原含量显著高于对照组,分别为肺静脉3301．97±309．70对1404．56±178．02、左心房峡部2477．86±190．43对1479．20±187．17、右心耳2045．92±139．43对1417．07±139．43。房颤组Ⅲ型胶原的含量肺静脉组织显著高于左房峡部,左房峡部显著高于右心耳（P〈0．05）,且存在明显的梯度差。结论：快速心房起搏可导致肺静脉和心房组织纤维化程度增加,发生结构重构。肺静脉、左房峡部和右心耳心肌纤维化的程度存在显著的梯度差异,可能是结构重构的关键部位,在房颤维持过程中起重要作用。