冠心病心肌缺血的血管生成研究概况

促进缺血心肌区域侧支循环的建立健全和动脉血管的新生 ,即治疗性血管生成 ,是目前国际心血管病学界的研究热点。从近几年的文献来看 ,主要通过冠脉造影方法 ,证实了冠脉侧支循环对冠心病病人的心脏保护作用。同时 ,发现血管生成生长因子可诱导血管生成 ,促进侧支循环建立。中医学在“生脉”方面具有丰富的理论基础 ,关于中药的血管生成活性及其对心肌缺血保护作用的研究 ,也取得了一定进展 ,为冠心病的中医药研究提供了新的途径。1　治疗性血管生成、血管生成与冠脉侧支循环治疗性血管生成包括血管生成和动脉新生。血管生成是指心肌内侧支…     

冠状动脉侧支循环评估方法

冠心病,是指由于冠状动脉粥样硬化(或)和功能改变(如痉挛)导致心肌血液供应减少或中断而产生的一组临床症候群。冠状动脉的反复或慢性缺血会引发侧支循环的产生,从而在一定程度上增加冠脉血流储备,缩小受损心肌的面积,降低急性冠脉事件后的死亡率,这为冠心病的治疗提供了一个新的方向。而如何评估冠脉侧支循环的作用,并根据评估结果制定相应的治疗方案也成为研究的重点之一。本文主要就近年来冠脉侧支循环的评估方法进行总结。     

血管新生与冠状动脉侧支循环

目前 ,冠心病的防治研究已从单纯改变病变血管供血转向如何促进侧支循环建立 ,血管新生与冠状动脉侧支循环的建立的关系倍受关注 ;还发现了某些对冠脉侧支循环建立有影响的药物 ,作者就此内容作一综述。     

冠脉侧支循环影响因素的研究进展

对于严重的冠状动脉粥样硬化性心脏病(冠心病)患者,再血管化治疗是其主要治疗方式.在冠状动脉造影中发现,某些患者存在自身形成的侧支循环,而某些人却未见侧支循环形成.侧支循环的形成对于冠心病患者症状和预后的改善有明确的益处,但这其中出现差异的原因目前尚无定论.现有的研究提示,冠脉侧支循环的形成可能与冠心病危险因素、细胞因子和药物相关.     

VEGF基因治疗冠心病的现状

近年来 ,随着冠心病监护系统的建立、溶栓治疗、经皮腔内冠状动脉成形术 (PTCA)、冠状动脉内支架植入(ICS)及冠状动脉旁路移植术 (CABG)治疗技术的应用 ,冠心病患者的死亡率已呈明显下降。但是 ,PTCA术后再狭窄 ,CABG血管狭窄 ,冠状血管多支弥漫性病变等仍待解决。目前一种新的治疗手段 -血管新生疗法 ,通过促进心肌缺血小血管生长和侧支循环形成 ,为这类患者的治疗带来新的希望 ,血管内皮生长因子 (VEGF)是目前公认的最具有特异性而强大的促进新生血管形成的生长因子 ,现对 VEGF基因治疗冠心病的进展综述如下。1　 VEGF的生物…     

关于冠脉侧支循环影响因素的研究进展

冠脉侧支循环(coronary collateral circulation,CCC)是指同一或不同冠脉血管之间相互吻合的微小血管。这些微小血管在冠状动脉狭窄的情况下有重塑和扩张的潜能,为受损心肌提供了另一种血液供应来源。侧支循环对冠心病患者有保护作用,即减小心肌坏死面积,保护心脏功能,减少心室扩张,减少室壁瘤的发生等。临床上发现,冠心病人群中侧支生成开放与否存在很大差异。目前对于引起不同个体之间侧支生成差异的影响因素存在争议。本文就冠状动脉侧支生成的机制,各因素与侧支生成的相关性进行综述。     

血管内皮生长因子基因治疗小型猪冠状动脉闭塞的实验研究

目的探讨应用血管内皮生长因子(VEGF)基因治疗动物实验性冠状动脉闭塞的疗效.方法中国实验用小型猪19只,结扎左冠状动脉前降支中远段,心肌内多点注射自行构建的pcD2/hVEGF121真核表达质粒.应用逆转录聚合酶链反应、VEGF免疫组化染色、Ⅷ因子相关抗原免疫组化染色等方法检测VEGF基因在心肌中的表达及其生物学作用,用常规冠状动脉造影观察VEGF基因治疗对闭塞冠脉侧支循环建立的作用.结果转移VEGF基因后,小型猪心肌内VEGF mRNA高表达,VEGF免疫组化染色提示VEGF蛋白表达水平升高;Ⅷ因子相关抗原免疫组化染色显示心肌毛细血管增加;冠状动脉造影证明VEGF基因治疗能够促进闭塞冠脉侧支循环的建立.结论心肌内注射pcD2/hVEGF121真核表达质粒能够获得VEGF mRNA和蛋白的有效表达,促进心肌毛细血管增生,促进侧支循环建立.     

冠状动脉侧支循环形成的研究进展

正在冠状动脉(冠脉)闭塞后侧支血流可能足以满足部分患者休息时的心肌需求,但普遍认为侧支循环通常不足以满足运动时的心肌需求,并且可能无法预防冠脉闭塞时的心肌缺血。为了预防急性血管闭塞期间的心肌缺血,通常认为20%～25%的流量足以提供静息所需的血液供应~([1]),约1/4的无冠脉粥样硬化性心脏病(冠心病)患者及1/3的冠心病患者有冠脉侧支循环形成~([2]),尚不清楚,但遗传因素可能起到相应作用~([3])。     

冠状动脉侧支循环的研究现状

侧支循环能够在冠状动脉(冠脉)严重狭窄或闭塞时保护心肌,保留相对更好的心肌收缩力,同时可以减轻缺血症状。当前冠心病的治疗主要包括药物治疗、经皮冠状动脉介入治疗(PCI)和冠状动脉旁路移植术(CABG)。然而,弥漫的慢性冠脉闭塞性病变或远端细小血管病变的患者通常不适合进行PCI或CABG。该组人群可表现为劳力性心绞痛和行动受限,但仍能保持较好的左心室功能,并维持一定的生活质量,其关键原因是大都存在侧支循环。治疗性侧支化(therapeutic collateralization)将可能会成为辅助治疗冠心病的切实可行的方法。本文主要阐述现阶段冠状动…     

冠状动脉侧支生长机制和潜在的治疗靶点

诱导冠状动脉侧支循环生长即治疗性血管新生是冠心病有效的治疗方法,但冠状动脉侧支生长是一个复杂的过程,与多种因素相关。虽然在动物实验中取得了较好的结果,但现有的临床试验未能复制这些结果。切实可行的临床治疗方案仍有待于对冠脉侧支生长机制的进一步研究。     

Therapeutic angiogenesis: a fantastic new adventure

A significant proportion of patients with coronary artery disease have symptoms refractory to medical treatment, yet are unsuitable for conventional revascularization techniques, like percutaneous coronary intervention and coronary artery bypass surgery. Such patients are potential candidates for alternative forms of coronary revascularization, like therapeutic angiogenesis. This strategy is designed to promote the development of supplemental collateral blood vessels that will act as endogenous bypass conduits. Two major avenues for achieving therapeutic angiogenesis are currently under intense investigation: gene therapy (the introduction of new genetic material into somatic cells to synthesize proteins that are missing, defective, or desired for specific therapeutic purposes) and protein-based therapy (administration of the growth factors, instead of the genes encoding for the growth factors responsible for angiogenesis). This article provides a concise review of the "components" of gene and protein-based therapy, namely, the growth factors, the vector (for gene therapy), the route of delivery, the therapeutic target, the desired therapeutic effect, and quantifiable clinical end points for trials of angiogenesis. Based on preliminary studies, the authors believe that therapeutic angiogenesis represents a promising novel therapy for treatment of the ischemic heart. In the future, angiogenesis will likely be offered as an adjunct to conventional revascularization strategies in subsets of patients who are only "suboptimally" revascularized with conventional techniques, and might evolve into a stand-alone treatment for some patients with nonrevascularizable disease.     

Good collaterals predict viable myocardium

The authors undertook this study to see whether highly developed coronary collaterals at an area shed by a totally occluded coronary artery predicts myocardial viability. Percutaneous coronary intervention (PCI) of a totally occluded coronary artery has been debated since its introduction. It is recommended to search for viable myocardium before opening a totally occluded coronary artery; however, there is no practical yet sensitive method of assessing myocardial viability in the catheterization laboratory. Forty-seven consecutive patients (12 women, 25.5%; 35 men, 74.5%), each with 1 totally occluded coronary artery, were prospectively enrolled to the study. After the diagnostic coronary angiography, all patients underwent dobutamine stress echocardiography to determine viable myocardium at the territory of the totally occluded coronary artery, and the status of angiographic coronary collaterals was assessed. Patients were then divided into 2 groups according to the presence (Group A) or absence (Group B) of viable myocardium by stress echocardiography. Eighteen patients (38.3%) had viable myocardium (Group A) in the area shed by the totally occluded coronary artery and 29 patients (61.7%) had nonviable myocardium (Group B). The incidences of significant coronary collateral circulation to the viable (Group A) and nonviable (Group B) areas were 66.7% (12 patients) and 20.7% (6 patients), respectively (p = 0.002). Logistic regression analysis was used to evaluate the independent factors for viable myocardium, and only significant coronary collateral circulation was found to be an independent factor for the detection of viable myocardium (p = 0.006, OR 16.7, 95% CI 2.25 to 124.4). The sensitivity and specificity of good collateral circulation for the detection of viable myocardium were 75% and 65.7%, respectively. The positive predictive and negative predictive values of the good coronary collateral circulation in detecting viable myocardium were 75% and 79%, respectively. The authors conclude that good coronary collaterals have a high sensitivity and positive predictive value for the prediction of viability as shown by dobutamine echocardiography, and only by assessing the coronary collateral circulation can one decide for percutaneous coronary revascularization, if not for coronary artery bypass surgery.     

冠心病患者冠状动脉侧支循环形成的相关因素

目的:探讨冠状动脉侧支循环形成的意义及影响侧支循环形成的相关因素。方法:冠状动脉造影中发现有侧支循环形成者47例作为研究组,以病变程度相同但无侧支循环形成者58例作为对照组;同时超声心动图检查病变局部室壁运动情况。结果:侧支循环形成与糖尿病、吸烟呈负相关,与服用他汀类药物呈正相关,而与性别、年龄、胸痛时间、有无高血压病、有无高脂血症、家族史、冠状动脉病变支数、服用ACEI类、硝酸酯类药物无关。结论:侧支循环多出现在病变严重的冠心病患者,糖尿病、吸烟是侧支循环形成的不利因素,服用他汀类药物能促进侧支循环形成;糖尿病患者即使形成侧支循环,对心功能的保护作用也较差。     

Percutaneous coronary intervention versus coronary artery bypass grafting: clinical outcomes in multivessel coronary artery disease

Revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is superior to medical management in reducing symptoms and prolonging exercise duration in patients with coronary artery disease (CAD). Ten randomized trials have compared the outcomes in percutaneous and surgically treated patients with multivessel CAD. The purpose of this article was to summarize the results of those trials to make recommendations regarding appropriate revascularization strategy.     

Expanding roles of the cardiovascular specialists in panvascular disease prevention and treatment

Atherosclerosis manifests as a broad spectrum of clinical pathology involving both coronary and noncoronary circulation. Peripheral artery disease (PAD) and coronary artery disease (CAD) have an important negative impact on each other with respect to treatment options and prognosis. The issue is further compounded by the underdiagnosis and undertreatment of PAD among CAD patients. There are compelling reasons why cardiovascular specialists should take an active role in the care of patients with global atherosclerotic disease. Several areas that impact cardiac patient care and thus are of particular interest to the cardiologists are renal artery disease causing hypertension or renal insufficiency; carotid artery stenosis in precoronary bypass patients; subclavian artery disease causing myocardial ischemia in patients with internal mammary bypass graft; and aortoiliofemoral arterial obstruction causing reduction in exercise tolerence and limitation in arterial access. Risk factor modifications for primary and secondary prevention are similar between CAD and PAD. Moreover, interventional cardiologists possess the necessary skills, which are transferable from coronary intervention to peripheral revascularization. To optimize outcomes, it is important for cardiovascular specialists to have a good foundation of knowledge about the natural history, treatment options and lesion selection. Collaboration with multidisciplinary specialists, including vascular surgeons and neurologists, is advisable for the treatment of PAD.     

PCI和CABG治疗单纯左主干病变效果进展

随着基础医学、医疗设备、高新技术的进展和循证医学的广泛开展,血运重建技术已经取得了快速的进展。左主干病变可通过内科和外科手段实现心肌血运重建,缓解症状,改善预后和延长寿命。目前血运重建措施有经皮冠状动脉介入治疗(PCI)和冠状动脉旁路移植术(CABG)。但是对于更适当的治疗措施尚无定论。故本文就PCI和CABG在左主干病变患者的治疗效果做一综述。     

Reduced pericardial levels of endostatin correlate with collateral development in patients with ischemic heart disease

OBJECTIVES: We investigated whether pericardial levels of a pro-angiogenic factor (vascular endothelial growth factor, VEGF) or an anti-angiogenic factor (endostatin) related to the presence of coronary collateral circulation in patients with significant coronary artery disease (CAD). BACKGROUND: Coronary collateralization favorably alters the prognosis of patients with occlusive CAD. The specific factors that mediate and maintain collateral formation in coronary vessel occlusion are yet to be identified. METHODS: Coronary angiograms from 39 patients undergoing coronary artery bypass surgery were evaluated for the absence of collaterals (n = 20) or the presence of Rentrop classification grade 3 collaterals (n = 19). Pericardial fluid samples were obtained at the time of surgery and were assayed for the VEGF and endostatin by enzyme-linked immunosorbent assay comparing the two groups of patients. RESULTS: Vascular endothelial growth factor levels were not significantly different between the groups (28.86 +/- 4.67 pg/ml vs. 24.39 +/- 3.08 pg/ml, p = 0.43). However, pericardial fluid endostatin levels were nearly 40% lower in patients with grade 3 collateralization compared with those lacking angiographic evidence of collaterals (15.17 +/- 1.87 ng/ml vs. 24.25 +/- 2.08 ng/ml, p < 0.0025). CONCLUSIONS: Pericardial fluid levels of endostatin, but not VEGF, are associated with the presence or absence of collaterals in patients with CAD. These data suggest that the angiogenesis inhibitor endostatin levels may locally modulate coronary collateral formation.     

Coronary Revascularization in Patients With Advanced Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have an increased risk of obstructive coronary artery disease (CAD), whereas patients with end stage renal disease who are receiving hemodialysis represent a population at particularly high risk of developing cardiac ischemic events. Patients with CKD and acute coronary syndromes should be treated the same way as acute coronary syndromes patients without kidney dysfunction. The benefit of revascularization in patients with advanced kidney failure and CAD is unknown. Observational studies suggest that revascularization might confer a survival benefit compared with medical therapy alone. Little evidence from randomized trials exists regarding the effectiveness of revascularization of patients with CAD with either coronary artery bypass grafting or percutaneous coronary intervention vs medical therapy alone in patients with CKD. The risk of contrast-induced nephropathy is a major concern when percutaneous coronary intervention is performed in patients with CKD. Strict rehydration protocols and techniques to minimize contrast use are paramount to reduce this risk. Finally, in CKD patients who are awaiting kidney transplantation, a noninvasive or invasive CAD screening approach according to the cardiovascular risk profile should be used. Revascularization should be performed in candidates with critical lesions.     

Regression of intercoronary collateral vessels in mongrel dogs after coronary bypass grafting

Four dogs underwent direct revascularization of a chronically occluded circumflex artery with an internal mammary artery bypass graft. Preoperative coronary cineangiograms demonstrated well developed intercoronary collateral vessels supplying the circumflex arterial bed. Intraoperative measurements of retrograde circumflex arterial flow and pressure were consistent with the presence of large collateral vessels. Closed chest postoperative estimates of the potential collateral circulation were obtained by advancing a Judkins catheter to the internal mammary wedge position. The graft wedge pressure was equated to the retrograde circumflex pressure. After coronary bypass grafting, the interval coronary angiographic and hemodynamic studies indicated that well developed collateral vessels regressed within the first postoperative month to capacities in the range of those found in normal dogs.     

Revascularization in Heart Failure: Coronary Bypass or Percutaneous Coronary Intervention?

Coronary artery disease (CAD) is the most common cause of heart failure in Western countries. Selected patients who have low left ventricular ejection fraction (LVEF) and CAD clearly benefit from coronary revascularization with coronary artery bypass grafting (CABG). CABG results seem to be superior to percutaneous coronary intervention (PCI) in the few comparative studies of the two approaches in patients who have CAD and low LVEF completed to date. Clinical improvement should be expected in most patients who undergo CABG. This is important for patients who have a limited life span that they could spend with a good functional status rather than being hospitalized for multiple repeat PCIs or symptomatic deterioration.