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…     

冠状动脉侧支循环研究进展

冠状动脉侧支循环作为替代血管为缺血心肌提供血液供应,减少心肌梗死面积、保护心功能,减少心绞痛症状发作,降低心血管不良事件发生,为无法行再血管化治疗的严重冠心病患者带来临床获益。现综述冠状动脉侧支循环调控因素的研究进展。     

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。     

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.     

冠心病的“生物搭桥”疗法

冠状动脉旁路移植术(CABG)和经皮冠状动脉腔内成形术(PTCA)是目前治疗冠心病的有效血管重建方法,这些方法主要靠侵入式恢复冠脉血流,存在费用高、术后再狭窄及无组织复流等问题.伴随血管新生分子机制研究的进一步深入,生物因子注射、干细胞移植和中药干预等多种疗法被应用于促进心肌血管再生和冠脉侧支循环的建立上,人们把这种通过生物因子、细胞及药物对血管生成或发生进行调控和干预,以其促进缺血心肌血管新生,增加侧支循环,改善心肌组织血流供应的方法称为“生物搭桥”.目前,治疗性血管新生已成为冠心病研究普遍关注的焦点,为冠心病治疗带来了新的希望.     

冠状动脉侧支循环研究进展

冠状动脉（冠脉）侧支循环为阻塞远端心肌提供重要的血液供应,因此具有保护缺血心肌的作用。近年来,对影响冠脉侧支形成的临床和生化因素进行了大量的研究,同时探讨了利用增加冠脉侧支循环治疗急性或慢性冠脉阻塞的潜在临床前景。该文简要介绍冠脉侧支循环的心肌保护作用、形成机制、临床影响因素以及治疗策略。     

腺苷负荷心肌核素显像评价冠脉慢性完全闭塞病变存活心肌的临床研究

目的应用腺苷负荷201Tl心肌灌注显像评价冠心病慢性血管闭塞相关区域存活心肌的准确性和安全性。方法 30例经16层CT冠状动脉成像(CTA)检查证实为冠心病慢性血管闭塞病变患者,经皮冠脉介入治疗(PCI)术前行腺苷负荷心肌核素显像检查。按恒定速度静脉注射腺苷(0.14mg·kg-1.min-1),在开始注射腺苷后第3分钟末静脉注射201Tl111MBq(3mCi),至开始注射腺苷后第6分钟末停止腺苷注入。10min后采集负荷相,3h后采集再分布影像。所有患者同期(1周内)均行冠状动脉造影术(CAG)检查。结果 30例经冠脉CTA证实为冠状动脉慢性完全闭塞病变(CTO)的患者中,CAG证实其中21例存在侧支循环,9例无侧支循环,按照CAG检查确定是否存在侧支循环分为侧支循环阳性组和侧支循环阴性组,分别对两组各节段负荷显像与延迟显像积分相减得出积分差。结果发现,存在侧支循环组患者平均积分差值为1.03±0.84,没有侧支循环组患者平均积分差值为0.31±0.56(P=0.033),差异具有统计学意义。结论腺苷负荷201Tl心肌灌注显像可以很好地评价冠心病慢性血管闭塞相关区域存活心肌。各节段负荷显像与延迟显像积分差越大,存活心肌越多,且与是否存在侧支循环有关。     

冠状动脉侧支循环某些相关因素的临床研究

目的研究冠状动脉侧支循环在冠状动脉完全闭塞与次全闭塞血管病变中的形成情况,观察心肌梗死病史、心肌肥厚及糖尿病对侧支循环形成的影响以及侧支循环对心肌的保护作用。方法回顾分析了我院一年内409例经冠状动脉造影证实的冠状动脉完全或次全闭塞患者,先按有无心肌梗死病史将患者分为两组,对照分析侧支循环形成的良好率,及心功能相关因素方面的差异。再按有无心肌肥厚、有无糖尿病病史分别分为两组,观察其对侧支循环形成的影响。结果冠状动脉完全与次全闭塞对比侧支循环形成的良好率有显著差异。有心肌梗死与无心肌梗死病史两组侧支循环形成的良好率比较无显著差异。两组的左心室舒张末期内径、左心室射血分数、室壁运动异常发生率及室壁瘤形成均有显著差异。而有心肌梗死病史者侧支循环良好组与不良组比较左心室舒张末期内径、左心室射血分数无差异。有无心肌肥厚对侧支循环形成良好率无差异。有糖尿病史者侧支循环血流良好率明显高于无糖尿病史者,且有显著差异。结论冠状动脉侧支循环的开放依赖于冠状动脉血管的完全或次全闭塞。冠状动脉缓慢闭塞下形成的侧支循环对心肌、心功能有保护作用。糖尿病有利于侧支循环的发展。     

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…     

冠状动脉侧支血管出现与发展影响因素的探讨

目的:探讨冠状动脉(冠脉)侧支血管出现与发展的影响因素.方法:经冠脉造影观察180例冠心病患者的侧支血管出现情况,对比其发展程度与心肌缺血病程、冠脉闭塞部位、冠脉病变程度及高血压病、糖尿病等合并症的关系.结果:侧支血管仅见于冠脉次全闭塞或完全闭塞的冠脉,心肌缺血病程长、右冠脉闭塞、无高血压病、糖尿病等合并症者侧支血管发展良好(P<0.01),闭塞或次全闭塞冠脉外血管的病变程度则与侧支血管的发展关系不大(P>0.05).结论:侧支血管出现提示有严重冠脉病变,慢性长期的心肌缺血可促进侧支血管的发展,高血压病、糖尿病等合并症是侧支血管发展的不利因素.     

磁共振延迟扫描缺血性心脏病的诊断价值

目的　研究延迟扫描序列诊断缺血性心脏病的价值。方法　采用 1.5T磁共振扫描仪行延迟扫描序列 ,并行冠状动脉造影。结果　冠状动脉造影显示 ,2 1例患者 4 0支冠状动脉呈不同程度狭窄。延迟扫描序列显示其中 16例的 2 5支 (6 2 .5 % )心肌节段呈高信号。 16例中 11例临床诊断心绞痛患者延迟扫描阳性。 15支狭窄冠状动脉 (11支闭塞 )有侧支循环形成 ,延迟扫描显示 14支相应心肌节段阳性 ;2 5支狭窄冠状动脉 (1支闭塞 )无侧支循环 ,11支相应心肌节段呈高信号 ,两者延迟扫描阳性率差异有显著性意义 (Fisher精确检验P <0 .0 0 1)。结论　延迟扫描序列是检出心肌梗死的有效方法。冠状动脉闭塞有侧支循环形成的心肌节段较非闭塞、无侧支循环形成的心肌节段延迟扫描序列阳性率高     

老年冠心病患者冠状动脉病变程度及其侧支循环对左室舒张功能的影响

目的　探讨老年冠心病患者冠状动脉病变程度及侧支循环对左室舒张功能 (LVDF)的影响。方法　 6 8例选择性冠状动脉造影主要分支狭窄≥ 75 %的老年冠心病患者作Leaman冠状动脉记分 ,左室造影测左室射血分数 (LVEF) ,左室壁运动作Cortina记分 ,经胸多谱勒超声血流仪测LVDF ,研究侧支循环对Leaman冠状动脉记分与LVEF、LVDF及Cortina记分间关系的影响。结果　全组Leaman冠状动脉记分与LVEF及Cortina左室壁运动记分无相关 ,与LVDF相关。有侧支循环建立两亚组LVDF差异无显著性意义 ,无侧支循环建立两亚组LVDF差异有显著性意义。结论　老年冠心病患者冠状动脉病变程度与LVDF有关 ,侧支循环的建立对老年冠心病患者的LVDF有保护作用。     

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。     

Blood flow velocity in donor coronary artery depends on the degree and pattern of collateral vessel development: a study using thrombolysis in myocardial infarction frame count method.

To understand the influence of collateral vessels on the coronary flow, TIMI frame count (TFC) method was applied as a measure of mean coronary blood flow velocity in artery giving collateral blood supply to the other artery in angiograms of 76 patients with single occluded coronary artery: RCA giving collaterals to occluded LAD or LAD giving collaterals to occluded RCA. As a control group, TFC was applied in angiograms of 30 patients with mild or no coronary artery disease. TFC was lower (faster blood flow) in LAD giving collaterals to occluded RCA (43 patients) than in LAD in control group (21.8 +/- 10.5 vs. 33.9 +/- 20.8 frames; P < 0.01). Higher degree of collateral vessels (Rentrop classification) and mixed- and distal-type collaterals (through the interventricular septum and heart apex) was associated with lower TFC. There was no difference in TFC in the RCA giving collaterals to an occluded LAD (33 patients) compared to the TFC in RCA in control group (16.6 +/- 9.0 vs. 18.5 +/- 6.0; P = NS), even in angiograms with higher degree of collateral vessel development. TFC was lower (faster blood flow) only in subgroups with mixed (proximal and distal types together in the same patient) and distal (through the interventricular septum and the apex of the heart) collateral types. A delayed contrast appearance in occluded LAD compared to occluded RCA has been found (35.1 +/- 16.1 vs. 20.2 +/- 7.3 frames; P < 0.001) with earlier contrast appearance in occluded LAD when proximal collateral vessels (through the conal and acute marginal branches of RCA) were presented. The coronary flow in donor arteries depends not only on the degree but also on the pattern of collateral vessels. The simple TFC method may facilitate the study of collateral filling pattern and offer insight into the influence of collaterals on the ventricular function.     

Effects of intracoronary injection of acetylcholine on coronary collateral circulation

To clarify the effect of intracoronary injection of acetylcholine on coronary collateral circulation, acetylcholine (20 and 50 μg) was injected directly into the donor artery of 5 patients with rest angina who had angiographically demonstrable collateral channels. Coronary spasm was defined as severe vasoconstriction (≥ 90% of luminal diameter) with chest pain and/or ischemic ST-segment changes. The intracoronary injection of acetylcholine induced spasm in all the 5 patients. The site of spasm was collateral vessels in 3, and the recipient coronary artery in 2 of the 5 patients. The spasm resolved spontaneously without administration of nitroglycerin. The contralateral intracoronary injection of acetylcholine also induced diffuse coronary spasm in 4 patients. These findings indicate that collateral vessels and recipient coronary arteries of the collateral circulation are susceptible to acetylcholine. Impaired relaxation and vasospastic responses to acetylcholine presumably due to endothelial dysfunction in the collateral and recipient coronary vessels may explain, at least in part, myocardial ischemia in patients with a well-developed collateral circulation. © 1993 Wiley-Liss, Inc.     

Influence of coronary collateral vessels on the results of thallium-201 myocardial stress imaging.

Although collateral vessels are commonly seen in patients with coronary disease, their functional significance has been debated. In this study segmental analysis of thallium-201 perfusion scintigrams obtained at rest and after exercise was made in 124 patients with angiographically proved coronary artery disease to determine whether collateral vessels could provide protection front myocardial ischemia during stress. All 15 coronary arteries that were completely occluded and had no collateral vessels showed a corresponding stress perfusion abnormality, but only 65 of 92 occluded arteries with angiographically visualized collateral vessels showed a corresponding stress defect (P < 0.05). In 13 hearts with stenosed arteries (more than 50 percent narrowing) without collateral vessels, the scintigraphic region supplied by the most severely stenosed vessel always became abnormal. When collateral vessels were present only 19 of 29 such regions showed a stress-induced perfusion defect (P < 0.05). The 10 protected scintigraphic areas were supplied in eight cases by collateral vessels originating from nondiseased arteries (nonjeopardized) and in two cases by collateral vessels that originated distal to a significant arterial stenosis (jeopardized). Fourteen of the 19 arteries that failed to show protection were supplied by jeopardized collateral vessels. The results (1) demonstrate that nonjeopardized coronary collateral vessels may account for a normal-appearing thallium-201 scintigram in segments supplied by severely narrowed coronary arteries, and (2) suggest that coronary collateral vessels çan provide, at least relative protection from stress-induced ischemia.     

Complete occlusion of the left main coronary artery: clinical and angiographic observations in five cases

Involvement of the left main coronary artery is observed in approximately 5 to 8% of patients with coronary artery lesions detected by coronary angiography, but occlusion of the left main artery is a very infrequent finding. Out of approximately 4000 patients undergoing coronary angiography, four men and one woman, 37 to 60 years old, showed total occlusion of this vessel. Four of them had angina pectoris and three had had a myocardial infarction. All five showed deep ST depression in V 2(or 3)-6 during bicycle exercise testing. Apart from the left main artery occlusion, all had significant obstructive lesions in other coronary vessels, including the right coronary artery or its major branches. There was collateral circulation from the right coronary artery in all patients. Left ventricular function was well preserved in three patients and markedly impaired in two. Four patients underwent bypass surgery and they have been followed for 10 to 28 months. Three are free of angina and one has only minimal angina. One patient refused surgery and he continued to have severe angina despite intense medical treatment. He died suddenly after 30 months follow-up. In patients with complete occlusion of the left main coronary artery, development of adequate collateral flow seems important in preserving left ventricular function, but collaterals are usually insufficient to prevent angina. Moreover, associated obstructive lesions in other coronary arteries constitute a potential threat to the collateral circulation. Effective symptomatic relief is obtained by coronary bypass grafting, and revascularization may also improve prognosis in this subset of patients with coronary heart disease.     

Myocardial viability in asynergic regions subtended by occluded coronary arteries: Relation to the status of collateral flow in patients with chronic coronary artery disease

Objectives. This study aimed to determine whether angiographically visualized collateral vessels in patients with chronic coronary artery disease imply the presence of viable myocardium in asynergic regions subtended by completely occluded coronary arteries.Background. Patients with chronic coronary artery disease who are being considered for revascularization frequently exhibit angiographically visualized collateral vessels to completely occluded coronary arteries supplying seventy asynergic myocardial regions. However, little is known about the relation between angiographic collateral flow and myocardial viability in these patients.Methods. We studied 42 patients with 78 completely occluded coronary arteries supplying asynergic territories. Angiographic collateral vessels were interpreted as absent (grade 1) in 14 patients, minimal (grade 2) in 27 and well developed (grade 3) in 37. Myocardial viability was determined with positron emission tomography using nitrogen-13 (N-13) ammonia and fluorine-18 (F-18) deoxyglucose lor assessment of regional perfusion and glucose uptake, respectively. Positron emission tomographic patterns were interpreted as mismatch (perfusion defect with enhanced F-18 deoxyghicose uptake); transmural match (severe concordant reduction or absence of both perfusion and F-18 deoxyglucose uptake) or nontransmural match (mild to moderate concordant reduction of both perfusion and F-18 deoxyglucose uptake).Results. There was no significant correlation (p = 0.14) between the severity of perfusion deficit assessed by positron emission tomography and the collateral grade. The extent of mismatch was unrelated to either the presence or the magnitude of collateral vessels. Conversely, with increasing collateral vessels from grade 1 to 3, the total extent of positron emission tomographic match remained similar, whereas the ratio of transmural to nontransmural match decreased. Myocardial viability was usually present in severely hypokinetic regions (82%). It was lower in akinetic-dyskinetic regions (49%). Of the 64 regions with angiographic collateral vessels, 37 (58%) (95% confidence interval [CI]46% to 70%) showed positron emission tomographic mismatch. In contrast, 7 (50%) of 14 (95% CI 24% to 76%) regions without collateral vessels on angiography exhibited positron emission tomographic mismatch. The presence of angtographically visualized collateral vessels was a sensitive (84%) but not specific (21%) marker of viability.Conclusions. In patients with chronic coronary artery disease, angtographically visualized collateral vessels to asynergc myocardial regions subtended by occluded coronary arteries do not always imply the presence of viable myocardium, suggesting that revascularization may not always provide a functional benefit.     

The Future of Collateral Artery Research

In the event of obstructive coronary artery disease, collateral arteries have been deemed an alternative blood source to preserve myocardial tissue perfusion and function. Monocytes play an important role in modulating this process, by local secretion of growth factors and extracellular matrix degrading enzymes. Extensive efforts have focused on developing compounds for augmenting the growth of collateral vessels (arteriogenesis). Nonetheless, clinical trials investigating the therapeutic potential of these compounds resulted in disappointing outcomes. Previous studies focused on developing compounds that stimulated collateral vessel growth by enhancing monocyte survival and activity. The limited success of these compounds in clinical studies, led to a paradigm shift in arteriogenesis research. Recent studies have shown genetic heterogeneity between CAD patients with sufficient and insufficient collateral vessels. The genetic predispositions in patients with poorly developed collateral vessels include overexpression of arteriogenesis inhibiting signaling pathways. New directions of arteriogenesis research focus on attempting to block such inhibitory pathways to ultimately promote arteriogenesis. Methods to detect collateral vessel growth are also critical in realizing the therapeutic potential of newly developed compounds. Traditional invasive measurements of intracoronary derived collateral flow index remain the gold standard in quantifying functional capacity of collateral vessels. However, advancements made in hybrid diagnostic imaging modalities will also prove to be advantageous in detecting the effects of pro-arteriogenic compounds.