Lean heart: Role of leptin in cardiac hypertrophy and metabolism

Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin’s role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity.     

Insights into the structure, distribution and function of the cardiac chloride channels.

This review describes the properties and distribution of the three major types of chloride currents that have been studied in cardiac tissue. These include a cAMP- and protein kinase A-dependent current, a calcium-activated current and a swelling-induced current. The study of cardiac anion currents is a less mature field than the study of cardiac cation currents. Consequently, less is known regarding the structure, molecular identity and physiological role of anion currents in comparison to cardiac cation currents. Where known, the available molecular and structural information is also discussed. Although there is no proven physiological role for cardiac chloride currents, the possible clinical electrophysiological roles of cardiac chloride currents are discussed.     

迷走神经在心律失常发生中的研究进展

作为遗传性心律失常之一的长QT综合征（LQTS）,现已发现有12型,其中在中国以LQT2为常见,可诱发尖端扭转型室性心动过速及室颤,临床上以反复发作的晕厥及常导致的猝死为特征。自主神经通过释放神经递质作用于受体调节离子通道,从而对某些心律失常起到一定的作用,而迷走神经通过直接或间接作用对多种心律失常具有一定的保护作用。本文主要对LQT2的研究进展、迷走神经与LQT2的关系以及其在心律失常中发挥的作用作一综述。     

Insulin-like growth factor I as a cardiac hormone: physiological and pathophysiological implications in heart disease

Accumulating evidence has indicated that insulin-like growth factor-1 (IGF-1) plays a specific role in the intricate cascade of events of cardiovascular function, in addition to its well established growth-promoting and metabolic effects. IGF-1 is believed to mediate many effects of growth hormone (GH), IGF-1 promotes cardiac growth, improves cardiac contractility, cardiac output, stroke volume, and ejection fraction. In humans, IGF-1 improves cardiac function after myocardial infarction by stimulating contractility and promoting tissue remodeling. Furthermore, IGF-1 facilitates glucose metabolism, lowers insulin levels, increases insulin sensitivity, and improves the lipid profile. These data suggest an attractive therapeutic potential of IGF-1. Both clinically observed and experimentally induced impairments of cardiac function are also found to be associated with abnormal IGF-1 levels. IGF-1 and its binding proteins have been considered as markers for the presence of certain cardiac abnormalities, indicating that IGF-1 may be a risk factor for certain cardiac disorders. The present review will emphasize the role of IGF-1 in the regulation of cardiac growth and function, and the potential pathophysiological role of IGF-1 in cardiac function.     

Cardiac angiosarcoma diagnosed and characterized by cardiac magnetic resonance imaging

Primary cardiac malignancies are rare. New imaging methods like cardiac magnetic resonance imaging (MRI) play an important role in the early diagnosis and differentiation of cardiac masses. By presenting the case of a 63-year-old woman with an angiosarcoma of the right atrium and its characteristic findings on cardiac MRI, the role of this new imaging method is emphasized.     

NLRP3炎性小体在心脏重构中的作用和进展

心脏重构是多重因素下所致的心脏结构和功能受损，炎症在心脏重构发生发展中起了重要作用，干预炎症有望成为新的治疗靶点，NLRP3炎性小体在心脏炎症中起了主导作用，本文通过概述NLRP3炎性小体在心脏重构中的作用，深入探讨其潜在的机制，以望给临床带来更多的策略。     

Postmenopausal hormone replacement therapy and the prevention of cardiovascular disease: a review

The role of hormone replacement therapy (HRT) for the prevention of cardiac disease is contentious. In this review the epidemiological evidence for the role of HRT in primary and secondary prevention of cardiac disease is assessed. Although current studies suggest very little role for HRT in women with established cardiac disease, its use in the 'healthy woman' without vascular disease until recently was not clear. HRT for the sole purpose of prevention of cardiac disease is now not indicated.     

Cardiac connexins as candidate genes for idiopathic atrial fibrillation

PURPOSE OF REVIEW: Atrial fibrillation is the most common sustained cardiac arrhythmia and may cause significant morbidity. Current management strategies offer only modest success and may be associated with intolerable drug side effects or risk of procedural complications. As with other cardiac arrhythmias, the identification of genetic determinants predisposing to atrial fibrillation may provide novel molecular targets for drug development. This review discusses the role of cardiac connexins in the heart and suggests that genetic defects in cardiac connexins may predispose to arrhythmia vulnerability. RECENT FINDINGS: Animal models deficient in cardiac connexins demonstrate abnormalities in myocardial tissue conduction and vulnerability to re-entrant arrhythmias, including ventricular tachycardia and atrial fibrillation. Atrial tissue analyses from human patients with atrial fibrillation consistently demonstrate alterations in connexin distribution and protein levels, suggesting a role of connexins in the perpetuation of the arrhythmia. Most recently, genetic studies of Cx43 and Cx40 indicate that genetic variations in these genes may predispose to arrhythmia vulnerability in humans. SUMMARY: Current data support the critical role of cardiac connexins in mediating coordinated electrical activation and conduction through myocardial tissue. Alterations in the tissue distribution or function of cardiac connexins may predispose to cardiac arrhythmias, supporting a previously proposed hypothesis that cardiac connexins should be considered a major therapeutic target in the management of atrial fibrillation.     

Bone morphogenetic protein-4: a novel therapeutic target for pathological cardiac hypertrophy/heart failure

Bone morphogenetic protein-4 (BMP4) is a member of the bone morphogenetic protein family which plays a key role in the bone formation and embryonic development. In addition to these predominate and well-studied effects, the growing evidences highlight BMP4 as an important factor in cardiovascular diseases, such as hypertension, pulmonary hypertension and valve disease. Our recent works demonstrated that BMP4 mediated cardiac hypertrophy, apoptosis, fibrosis and ion channel remodeling in pathological cardiac hypertrophy. In this review, we discussed the role of BMP4 in pathological cardiac hypertrophy, as well as the recent advances about BMP4 in cardiovascular diseases closely related to pathological cardiac hypertrophy/heart failure. We put forward that BMP4 is a novel therapeutic target for pathological cardiac hypertrophy/heart failure.     

Enhanced angiotensin II activity in heart failure: reevaluation of the counterregulatory hypothesis of receptor subtypes

There are strong data favoring the pathogenic role of angiotensin II type 1 receptor (AT(1)) activation with subsequent promotion of myocyte growth and cardiac fibrosis in the development of cardiac hypertrophy and heart failure. An emerging hypothesis suggests that the activity of the angiotensin II type 2 receptor (AT(2)) may counterregulate AT(1) receptor effects during cardiac development and during the evolution of cardiac hypertrophy and heart failure. In this review, we examine the potential role of AT(2) activity in the context of this hypothesis. In contrast to the counterregulatory hypothesis, studies in mice with an overabundance of, or a deficiency in, the AT(2) receptor do not suggest that AT(2) signaling is essential for cardiac development. Moreover, the proposed antigrowth effects of AT(2) receptor signaling in pathological cardiac hypertrophy could not be shown in two mice models both deficient in AT(2) receptors. The role of AT(2) receptor signaling in cardiac fibrosis is, however, still debatable because of conflicting data in the same two studies. In angiotensin II-evoked apoptosis in cardiomyocytes, the proposed proapoptotic role of AT(2) activity could not be confirmed. Furthermore, in the progression from the bench to bedside, the results of two large clinical trials in heart failure, namely ELITE II and Val-HeFT, can be explained without ascribing a major protective role to the unopposed activity of the AT(2) receptor in the failing myocardium. In this review, we conclude that the collective evidence does not strongly support a net beneficial effect of AT(2) stimulation in the diseased myocardium.     

The role of transesophageal echocardiography in the intraoperative period

The goal of hemodynamic monitoring and management during major surgery is to guarantee adequate organ perfusion, a major prerequisite for adequate tissue oxygenation and thus, end-organ function. Further, hemodynamic monitoring should serve to prevent, detect, and to effectively guide treatment of potentially life-threatening hemodynamic events, such as severe hypovolemia due to hemorrhage, or cardiac failure. The ideal monitoring device does not exist, but some conditions must be met: it should be easy and operator-independently to use; it should provide adequate, reproducible information in real time. In this review we discuss in particular the role of intraoperative use of transesophageal echocardiography (TOE). Although TOE has gained special relevance in cardiac surgery, its role in major non cardiac surgery is still to be determined. We particularly focus on its ability to provide measurements of cardiac output (CO), and its role to guide fluid therapy. Within the last decade, concepts oriented on optimizing stroke volume and cardiac output mainly by fluid administration and guided by continuous monitoring of cardiac output or so called functional parameters of cardiac preload gained particular attention. Although they are potentially linked to an increased amount of fluid infusion, recent data give evidence that such pre-emptive concepts of hemodynamic optimization result in a decrease in morbidity and mortality. As TOE allows a real time direct visualization of cardiac structures, other potentially important advantages of its use also outside the cardiac surgery operation room can be postulated, namely the ability to evaluate the anatomical and functional integrity of the left and the right heart chambers. Finally, a practical approach to TOE monitoring is presented, based on a local experience.     

Neuregulin as a Heart Failure Therapy and Mediator of Reverse Remodeling

The beta isoform of Neuregulin-1 (NRG-1β), along with its receptors (ErbB2–4), is required for cardiac development. NRG-1β, as well as the ErbB2 and ErbB4 receptors, is also essential for maintenance of adult heart function. These observations have led to its evaluation as a therapeutic for heart failure. Animal studies and ongoing clinical trials have demonstrated beneficial effects of two forms of recombinant NRG-1β on cardiac function. In addition to the possible role for recombinant NRG-1βs as heart failure therapies, endogenous NRG-1β/ErbB signaling appears to play a role in restoring cardiac function after injury. The potential mechanisms by which NRG-1β may act as both a therapy and a mediator of reverse remodeling remain incompletely understood. In addition to direct effects on cardiac myocytes NRG-1β acts on the vasculature, interstitium, cardiac fibroblasts, and hematopoietic and immune cells, which, collectively, may contribute to NRG-1β’s role in maintaining cardiac structure and function, as well as mediating reverse remodeling.     

The emerging role of microRNAs in cardiac remodeling and heart failure

Recent studies have suggested a potentially important role for a family of tiny regulatory RNAs, known as microRNAs (miRNAs or miRs), in the control of diverse aspects of cardiac function in health and disease. Although the field of miRNA biology is relatively new, there is emerging evidence that miRNAs may play an important role in the pathogenesis of heart failure through their ability to regulate the expression levels of genes that govern the process of adaptive and maladaptive cardiac remodeling. Here, we review the biology of miRNAs in relation to their role in modulating various aspects of the process of cardiac remodeling, as well as discuss the potential application of miRNA biology to the field of heart failure.     

培多普利抑制心肌重构的动物实验研究

目的:本研究采用Wistar大鼠冠脉结扎心梗后心衰模型,以培多普利作为观察药物,探讨肾素血管紧张素系统(RAS)在心肌重构中的地位和血管紧张素转换酶抑制剂(ACEI)对心肌重构的干预作用.方法:将Wistar大鼠分为梗塞组、梗塞治疗组和假术组.梗塞组结扎左冠状动脉,梗塞治疗组在前者基础上用培多普利治疗2mg/kg/天,假手术组不结扎左冠状动脉.三月后测血流动力学参数,血液及组织内血管紧张素Ⅱ(AngⅡ)含量、血管紧张素转换酶(ACE)活性和观察组织形态学变化.结果:三月后,与假术组相比,梗塞组出现了克血性心衰(DHF)的血流动力学改变;心肌局部AngⅡ含量、ACE活性显著差增高,但血液AngⅡ含量和ACE活性无明显改变;心脏重量指数显著上升;残存心肌细胞肥大,间质增生,胶原蛋白沉积.培多普利可以改善血流动力学参数,减少AngⅡ的生成、抑制ACE活性并减轻心肌细胞肥大、间质增生和胶原蛋白沉积的程度.结论:心肌组织局部的RAS参与了心肌重构的病理生理过程,血液RAS与心肌重构无显著相关,ACEI可以有效地防治心肌重构及心衰.     

The role of the implantable cardioverter-defibrillator for prevention of sudden cardiac death

Sudden cardiac death, which accounts for approximately 350,000 deaths each year, is a major health care problem. Antiarrhythmic drugs have not been reliable in preventing sudden cardiac death. Although beta-blockers, angiotensin-converting enzyme inhibitors, and revascularization play a role in prevention of sudden cardiac death, the development and subsequent refinement of the implantable cardioverter-defibrillator has made the most important contribution to its management. Several randomized, controlled trials have demonstrated improved survival in patients resuscitated from cardiac arrest. Two recent trials also suggest a role for primary prevention in selected patients with coronary artery disease, ventricular dysfunction, and nonsustained ventricular tachycardia in whom sustained ventricular tachycardia is induced. Further technological refinements and development of new, more sensitive risk stratifiers with a higher positive predictive value for sudden cardiac death will expand the indications for this life-saving therapy.     

瞬时受体电位C通道与心肌肥厚的研究进展

瞬时受体电位C(transient receptor potential canonical,TRPC)通道作为一类重要的非选择性阳离子通道，在心脏具有广泛的分布和表达。TRPC通道通过改变细胞膜电位和介导钙离子(Ca2+)内流对心脏的生理和病理反应产生重要影响。细胞内Ca2+不仅在心肌细胞的兴奋-收缩偶联中发挥重要作用，而且与各类心脏疾病发生密切相关。最近研究发现，TRPC通道可以通过调节细胞内Ca2+变化，与钙调磷酸酶(calcineurin,CaN)和活化的T细胞核因子(nuclear factor of activated T cells,NFAT)等效应因子参与心肌肥厚的发生发展过程，同时可诱导其他心脏疾病（如心肌纤维化、心率失常、心力衰竭）的发生。本文根据相关研究，围绕TRPC通道在心肌肥厚及相关心脏疾病的发生发展中的作用进行总结回顾。     

Advance practice nursing in heart transplantation

This article describes the role of the advanced practice nurse in the field of cardiac transplantation. A brief review of the history of cardiac transplantation is presented. The role of advanced practice nursing is evolving and changing to meet patients' needs in an increasingly complex health care environment. The advanced practice nurse is uniquely qualified to meet those needs in a variety of roles and settings. The advanced practice nurse maybe a clinical nurse specialist, nurse practitioner, nurse mid-wife, or nurse anesthetist. Each role must include the element of clinical practice in order to be considered advanced practice nurse described in this article. The advanced practice nurse was a clinical nurse specialist in the role of cardiac transplant coordinator. This role comprises the sub-roles of educator, clinician, consultant, researcher, and administrator. The responsibilities and challenges of each sub-role are discussed. Suggestions for the direction of future practice are also presented.     

Epsilon protein kinase C as a potential therapeutic target for the ischemic heart

Ischemic heart disease is the leading cause of morbidity and mortality in the western world. Ischemic damage can occur by acute myocardial infarction, stable angina, cardiac stunning, and myocardial hibernation. In addition, 'scheduled' ischemic events, occurring during cardiac surgery, heart transplantation, and elective angioplasty, can also result in cardiac damage. Ischemic or pharmacological preconditioning can decrease the extent of damage to the myocardium. Although the mechanism of preconditioning-mediated cardioprotection is not fully understood, epsilonPKC has been implicated as a critical mediator of this process in animal studies. The use of isozyme-specific pharmacological tools has permitted a better elucidation of the upstream stimuli and the downstream transducers of epsilonPKC in the pathways leading to cardioprotection. While little is known about the role of epsilonPKC in these pathways in humans, animal studies suggest a potential therapeutic role of epsilonPKC. This review will focus on the role of epsilonPKC in cardiac protection and on the signal transduction cascades that have been implicated in this protection.