心肌血管再生治疗技术的研究进展

缺血性心脏病发病率、致死率较高,且大约10%左右弥漫性冠脉病变的患者仍得不到有效治疗。近年来,基因及干细胞技术的发展为缺血性心脏病的治疗提供了新的方向。随着研究的深入,除了血管再生机制取得突破外,新技术新方法也得到了快速的发展。比如:干细胞治疗、细胞因子治疗、基因治疗、激光心肌血运重建术治疗、超声靶向破坏微泡造影剂以及多种方法联合治疗。文章就心肌血管再生治疗的技术方法进行综述。     

不同干细胞来源的外泌体在缺血性心脏病中的促血管新生作用

缺血性心脏病是指各种原因造成心肌供血量不足,导致氧气和营养物质供应不足,引起各种心脏功能障碍.促血管新生是治疗缺血性心脏病的一个关键因素.越来越多的研究表明,干细胞来源的外泌体作为一种细胞间相互作用的媒介,为缺血性心脏病的治疗提供了新的可能.现对各种干细胞来源的外泌体在治疗缺血性心脏病中促血管新生作用及机制做一综述.     

低能量体外冲击波治疗缺血性心脏病

缺血性心脏病是导致死亡的主要原因。低能量体外冲击波治疗可以通过增加血管内皮生长因子的mRNA的表达、增加心肌有效灌注和改善左室重塑,从而改善缺血性心脏病患者的症状,减少硝酸甘油的服用,达到治疗缺血性心脏病的目的。     

内皮祖细胞与缺血性心脏病

缺血性心脏病是一类严重威胁人类健康的疾患,其发生、发展和预后与血管内皮密切相关。研究发现内皮祖细胞也参与出生后的内皮修复和血管新生过程,提示其在缺血性心脏病中的重要治疗作用和临床运用前景。     

基因治疗缺血性心脏病的研究进展

缺血性心脏病严重威胁着人类的健康,尤其是严重的弥漫性病变,目前临床使用的治疗方法无法取得满意的疗效,根据血管生成的机制应用促血管生成因子、基因治疗等方式进行的治疗性血管生成为此类疾病的治愈带来了希望。本文就促血管生成因子基因治疗缺血性心脏病的研究进展进行综述。     

基于肠道菌群探讨心脾同治法治疗缺血性心脏病的机制

缺血性心脏病的发生发展严重影响人民的生命健康。心脾同治法,即益气活血健脾法,作为治疗缺血性心脏病的重要方法,符合缺血性心脏病气虚血瘀的本质。肠道菌群的生理功能与中医的脾脏关系密切,肠道菌群及其代谢产物影响缺血性心脏病的发生发展,心脾同治类中药通过肠道菌群改善缺血性心脏病的预后。本研究探讨心脾同治类中药通过抑制不良产物、促进血管新生、抗炎等方面改善心肌缺血缺氧的机制。     

促血管新生治疗的机制与应用

血管新生的过程与缺血、缺氧、炎症反应、生长因子和一氧化氮均有密切关系;心脏的血管新生对于改善缺血性心脏病的心肌灌注有着重要作用。动物实验和临床研究表明,促血管生成因子能够促进侧枝循环建立,可能为缺血性心脏病患者提供一种新的治疗方法。     

SDF—1／CXCR7 信号通路在缺血性心脏病中的作用机制与意义

基质细胞源性因子-1(SDF-1)/CXC趋化因子受体7(CXCR7)信号通路参与血管新生和炎性反应,在缺血性心脏病的发生发展、缺血部位的血管新生和修复过程中起重要作用。激活此通路,可提高干细胞移植成活率,改善移植治疗的效果,进而可能促进干细胞移植用于缺血性心脏病的治疗。SDF-1/CRCR7有望成为预防和治疗缺血性心脏病的新靶点。     

辛伐他汀对60例非缺血性心脏病心功能及心律失常的影响

辛伐他汀在血管治疗领域的降脂稳定斑块作用以及改善内皮功能、抑制平滑肌细胞增殖、抑制血小板功能、抑制血管的炎症反应等均得到临床证实[1,2],但对于他汀类药物治疗非缺血性心脏病并发心衰的观察较少,本研究主要观察他汀类药物在非缺血性心脏病并发心力衰竭治疗中对心功能、心律失常以及C反应蛋白(CRP)的影响,从而探讨他汀类药物对非缺血性心脏病的治疗作用.     

血管再生基因调控的研究现状和展望

随着生活水平的提高,冠状动脉性心脏病的发病率近年来呈增长趋势。再生的血管很大程度上改善心肌的供血,从而缓解疾病的进展。到目前为止,无论是在体内还是体外的研究中,促血管生成的细胞因子诱导血管再生大多是利用单一的血管生成因子。它的疗效还是有限的。近年来,对血管再生基因治疗的研究为缺血性心脏疾病的治疗提供了新的方向。随着基因工程的开展,基因重组技术与基因芯片技术的发展为血管再生在基因水平的研究创造了良好的基础,现就血管再生的基因治疗进行综述。     

Depression and ischemic heart disease: what have we learned from clinical trials?

PURPOSE OF REVIEW: Discuss the interplay of depression and ischemic heart disease. Studies demonstrate high prevalence of depression and its negative impact among patients with ischemic heart disease. RECENT FINDINGS: Results extend previous findings among men, demonstrating a significant increase in mortality and cardiovascular events among depressed women. Sertraline, citalopram and mitrazapine have been shown to be safe and well tolerated in patients with ischemic heart disease. Sertraline and citalopram have demonstrated efficacy for treating depression in such patients. Mirtazapine did not have significant efficacy on post-myocardial infarction depression. Cognitive-behavioral therapy and interpersonal therapy have not been found to have a significant treatment effect. Treating depression may have an impact on cardiovascular morbidity and mortality, but this has not yet been adequately studied. Studies to date lack sufficient statistical power to fully examine the impact of interventions for depression on cardiovascular outcomes. SUMMARY: Cardiologists encounter depression among 25-30% of their patients with ischemic heart disease. Depression is an independent risk factor for poor prognosis among ischemic heart disease patients, at a level comparable to several conventional cardiac risk factors. Adequate treatment of depression may improve the poor prognosis of depressed patients with ischemic heart disease.     

The Management of Chronic Ischemic Heart Disease in the Elderly

Despite advances in medical and surgical therapy, ischemic heart disease remains the most important cause of death and disability in an ever growing population. The management of elderly patients with ischemic heart disease is made more difficult by the presence of comorbid medical conditions, which can both further aggravate ischemic heart disease and interfere with pharmacological and interventional therapy. Despite the difficulties in the management of ischemic heart disease in the elderly, there is substantial evidence that older patients can benefit greatly from aggressive, rational treatment of this condition and, therefore, such treatment should not be denied solely on the grounds of age.     

Gene therapy for ischemic heart disease

Current pharmacologic therapy for ischemic heart disease suffers multiple limitations such as compliance issues and side effects of medications. Revascularization procedures often end with need for repeat procedures. Patients remain symptomatic despite maximal medical therapy. Gene therapy offers an attractive alternative to current pharmacologic therapies and may be beneficial in refractory disease. Gene therapy with isoforms of growth factors such as VEGF, FGF and HGF induces angiogenesis, decreases apoptosis and leads to protection in the ischemic heart. Stem cell therapy augmented with gene therapy used for myogenesis has proven to be beneficial in numerous animal models of myocardial ischemia. Gene therapy coding for antioxidants, eNOS, HSP, mitogen-activated protein kinase and numerous other anti apoptotic proteins have demonstrated significant cardioprotection in animal models. Clinical trials have demonstrated safety in humans apart from symptomatic and objective improvements in cardiac function. Current research efforts are aimed at refining various gene transfection techniques and regulation of gene expression in vivo in the heart and circulation to improve clinical outcomes in patients that suffer from ischemic heart disease. In this review article we will attempt to summarize the current state of both preclinical and clinical studies of gene therapy to combat myocardial ischemic disease. This article is part of a Special Section entitled “Special Section: Cardiovascular Gene Therapy”.     

Endothelin-1 concentrations in pericardial fluid are more elevated in patients with ischemic heart disease than in patients with nonischemic heart disease

There is epidemiologic evidence that the prognosis of patients with nonischemic heart failure is better than that for patients with ischemic heart failure. In addition, studies have revealed that patients with ischemic heart failure show a poorer response to medical therapy. However, the pathophysiologic difference between ischemic and nonischemic heart disease is unclear. To clarify this point, we measured atrial natriuretic peptide, brain natriuretic peptide, angiotensin II, endothelin (ET)-1. interleukin-1beta interleukin-6. tumor necrosis factor (TNF)-alpha soluble TNF receptor I, and soluble TNF receptor II concentrations in plasma and pericardial fluid in patients with ischemic or nonischemic heart disease undergoing cardiac surgery. The pericardial ET-1 concentration in patients with ischemic heart disease was statistically greater than that in patients with nonischemic heart disease (about 1.5-fold), although no difference was found in the plasma ET-1 concentration. These findings suggest that the production and secretion of ET-1 from the myocardium in patients with ischemic heart disease are augmented to a greater extent than in patients with nonischemic heart disease. This result may lead to a greater understanding of the pathophysiology of ischemic heart disease.     

New Information on the Role of Beta-Blockers in Cardiac Therapy

Summary. Hypertension and ischemic heart disease are important precursors of heart failure. The prevention of progression to heart failure is a prime objective when treating patients with hypertension or ischemic heart disease. In patients with hypertension, treatment with either diuretics or beta-blockers reduces the risk of chronic heart failure. In patients with ischemic heart disease, beta-blocker therapy reduces the risk of recurrent myocardial infarction and ensuing cardiac dysfunction. The beneficial effects of beta-blocker therapy may be greater in post-infarction patients who have impaired left ventricular function than in those patients without such impairment.When considering heart failure itself, the efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in patients with mild-to-severe left ventricular dysfunction and their use is indicated for all stages of heart failure to reduce symptoms and retard further impairment of left ventricular function. Diuretics and digitalis offer relief from the symptoms of the disease, while positive inotropes are reserved for parenteral administration in end-stage heart failure, as a bridge to transplantation, or in acute exacerbations of the disease. Added to standard therapy, beta-blockade is of value in the treatment of heart failure, preventing further deterioration and improving hemodynamics, exercise tolerance, quality of life, and long-term prognosis.     

体外震波治疗终末期冠心病

由于缺少有效的治疗方法,不具备冠脉介入或冠脉搭桥手术指征的终末期冠心病患者的预后是不良的。因此,迫切需要找到一种非侵入性治疗缺血性心脏病的有效疗法。尽管现在临床上还没有一种有效的药物或手术可以用功能性的可伸缩的组织替代受损的心肌,但是通过体内诱导血管生成来恢复或增加休眠心肌的伸缩性是完全可能的。国外的实验研究表明,体外心脏的震波疗法是治疗缺血性心脏病的一种有效而无任何创伤的全新疗法,能够使活体内血管再生因子及其受体表达上调,有促进缺血组织的血管新生和加速侧支循环建立的作用,为改善心肌缺血,治疗冠心病提供了新的思路和方法。现结合文献对体外震波治疗终末期冠心病的方法、研究现状、适应证、优缺点作一综述。     

The role of clopidogrel in the management of ischemic heart disease

PURPOSE OF REVIEW: Platelet inhibition remains a key component in the prevention and treatment of ischemic heart disease. This review documents recent advances in the use of clopidogrel for the management of myocardial ischemia. RECENT FINDINGS: For the prevention of ischemic heart disease, the addition of clopidogrel is not superior to aspirin alone at reducing short or long-term major adverse cardiac events. In patients with ST-segment elevation myocardial infarction who receive thrombolytics, clopidogrel therapy confers broad benefits including survival when initiated at the time of presentation. Long-term administration of clopidogrel is necessary to prevent thrombotic complications following coronary stent placement. Overall, there are no major safety concerns across the spectrum of cardiac indications for clopidogrel. SUMMARY: Clopidogrel has become a cornerstone of therapy in the treatment of acute ischemic coronary syndromes and as prevention of thrombosis after coronary stenting. It has demonstrated safety and efficacy in most aspects of ischemic heart disease. Questions remain about optimal duration of therapy following deployment of drug-eluting stents.     

Cell-based therapy for chronic ischemic heart disease--a clinical perspective

In patients with ischemic heart disease, the goal of cell therapy is to improve perfusion and function of the damaged heart muscle. For this review, we selected articles that reported the findings from the major clinical studies of cardiovascular stem cell therapy in patients with chronic ischemic heart disease. Because of the current status of development of clinical investigation in this field, all relevant studies were included. Initial clinical trials have shown that adult cell-based therapy is safe and may improve the quality of life and the functional status of patients with chronic myocardial ischemia. Adult bone marrow mononuclear cells have been most frequently used in cardiac cell therapy trials to date, but new cell types are now being assessed in both preclinical and clinical studies. Although not well defined, mechanisms underlying the benefits associated with cell therapy are most likely multiple and include a paracrine effect. Cell therapy in patients with chronic ischemic heart disease has been shown to be safe and feasible. Initial data have shown that cell therapy with autologous bone marrow cells is associated with modest functional improvements. This finding needs to be confirmed in subsequent phase 2 and 3 trials.     

Assessment of the use of various cardiac pacing modes for selection of antiarrhythmic therapy for prevention of recurrent attacks of atrial fibrillation and flutter

AIM: To determine optimal mode of transesophageal pacing for selection of appropriate antiarrhythmic therapy for prevention of attacks of atrial fibrillation and flutter in patients with ischemic heart disease. MATERIAL AND METHODS: Two hundred eighteen patients with ischemic heart disease and attacks of atrial fibrillation or flutter. Selection of antiarrhythmic drugs was carried out with the use of competitive, rapid, salvos of ultra rapid, and slowly accelerating ultra rapid modes of pacing. Results. Most effective and reproducible method for induction of attacks of atrial flutter and fibrillation was slowly accelerating ultra rapid mode of pacing. Average duration of positive clinical effect of preventive antiarrhythmic therapy selected basing on the results of this mode in patients with ischemic heart disease was 3.1-/+0.3 years. Unfavorable prognostic sign decreasing preventive effect of antiarrhythmic therapy was left atrial dilatation. CONCLUSION: Slowly accelerating mode of transesophageal pacing was most effective tool for selection of antiarrhythmic therapy aimed at prevention of attacks of atrial fibrillation and flutter in patients with ischemic heart disease.     

Comparison of the natural history of new onset and exacerbated chronic ischemic heart disease. The Chest Pain Study Group

To compare the natural history of patients with new onset ischemic heart disease with that of patients with exacerbations of chronic ischemic heart disease, short- and long-term outcomes of 3,465 emergency room patients with acute ischemic heart disease at four community and three university hospitals were evaluated. Acute myocardial infarction was diagnosed in 598 (33%) of the 1,835 patients with a prior history of infarction or angina and 934 (57%) of the 1,630 without such a history (p less than 0.001). Patients with new onset ischemic heart disease with acute myocardial infarction were more likely than patients with infarction and exacerbated chronic ischemic heart disease to have Q wave infarction (57% versus 36%) and to receive thrombolytic therapy (11% versus 5%); they also had higher maximal creatine kinase levels (1,088 +/- 1,299 versus 733 +/- 906 U/liter) (p less than 0.0001 for all three). After adjustment for differences in clinical presentation and initial triage, patients with new onset ischemic heart disease with acute myocardial infarction were less likely than the comparison group to have congestive complications (odds ratio 0.63, 95% confidence interval 0.47 to 0.84, p less than 0.01) but not less likely to have arrhythmic, ischemic or overall complications. Among patients with angina without acute myocardial infarction, patients with new onset ischemic heart disease were less likely to have recurrent ischemic pain and congestive heart failure. In multivariate analysis of long-term follow-up data on 457 patients from one hospital, patients with new onset ischemic heart disease had better cardiovascular survival rates.(ABSTRACT TRUNCATED AT 250 WORDS)