The heart in Tangier disease. Severe coronary atherosclerosis with near absence of high-density lipoprotein cholesterol.

Cardiac necropsy findings are described in a 72-year-old man with Tangier disease whose plasma total cholesterol levels averaged 70 mg/dL, low-density lipoprotein cholesterol level was 45 mg/dL, and high-density lipoprotein cholesterol level was 1.4 mg/dL, and who had coronary artery bypass grafting for severe atherosclerotic coronary artery disease. At necropsy, 24 of the 72 (33%) 5-mm segments of the 4 major (right, left main, left anterior descending, and left circumflex) native coronary arteries and 4 of the 27 (15%) 5-mm segments of the saphenous vein aortocoronary bypass conduits were narrowed by more than 75% in cross-sectional area by atherosclerotic plaques. The plaques were composed primarily (91% to 97%) of fibrous tissue. Oil red O staining, polarized light microscopy, and electron microscopy revealed cholesterol deposits in the plaques and in the walls of coronary arteries, saphenous vein grafts, and aorta. Such deposits also were found in foam cells of histiocytic origin, fibroblasts in all four cardiac valves, and in Schwann cells of cardiac nerves.     

Immunocytochemical investigation of atherosclerotic changes observed in aortocoronary bypass vein grafts using monoclonal antibodies

The authors have performed immunocytochemical surveys on atherosclerotic changes observed in saphenous vein aortocoronary bypass grafts, comparing the changes occurring in coronary and aortic lesions. The two monoclonal antibodies used in this study were obtained by T. Tsukada. One of them, named HHF35, exhibited specificity to smooth muscle cells; the other, named HAM56, was specific to macrophages. These immunocytochemical studies clearly demonstrated that cells encountered within the fibrous intimal thickening in the vein graft were inevitably smooth muscle cell in origin. Macrophages were seldom seen in the grafts examined. In contrast to vein grafts, macrophages were noted within the intima of all specimens from arterial atherosclerotic lesions obtained from the same patients. These studies suggest a difference in the progression of intimal thickening between the venous graft and the arterial atherosclerotic lesions.     

Structural features of cell death in atherosclerotic lesions affecting long-term aortocoronary saphenous vein bypass grafts

Aortocoronary saphenous vein bypass grafts fail because of structural pathologies (thrombosis, intimal hyperplasia and atherosclerosis) within the 'arterialized' vein leading to graft stenosis. This study examined structural characteristics of atherosclerotic alterations in long-term aortocoronary artery saphenous vein bypass grafts with particular attention to the features of cell death in atherosclerotic lesions. Stenotic vein grafts were obtained from 10 patients at redo coronary artery bypass grafting operations. All the grafts were affected by histological abnormalities, with eight out of ten grafts showing evidence of atherosclerotic alterations in the intimal hyperplastic layer. Areas containing foam cells were examined by electron microscopy. Cells with cytoplasmic lipid accumulations were characterized by varying degrees of chromatin condensation, fragmentation or dispersion, by focal areas of oedema and vacuolisation of their cytoplasm, and by plasmalemmal destruction. Some lipid-filled cells exhibiting signs of destruction contained myofilaments and basal membrane fragments, allowing them to be identified as smooth muscle cells. Macrophage foam cells were found to have undergone similar destruction. No cells showing nuclear degeneration were observed to have intact cytoplasmic organelles. Neither were apoptotic bodies identified, but necrotic remnants were frequently seen. The results suggest that cell death in atherosclerotic lesions affecting aortocoronary artery saphenous vein bypass grafts occurs through oncosis rather than by apoptosis.     

Electron-microscopic detection of apoptotic and necrotic cell death in non-atherosclerotic areas of stenotic aortocoronary saphenous vein bypass grafts

Aortocoronary saphenous vein bypass grafts undergo structural alterations within the arterialized vein, resulting in graft stenosis and failure. Areas of the acellular intima contribute to fissuring, cracking and ulceration, while areas of the media become highly vascular but thinned. This study aimed to examine the ultrastructural features of cell death, including apoptosis and necrosis, in non-atherosclerotic areas of the stenotic aortocoronary saphenous vein bypass grafts. Thirteen stenotic vein grafts were obtained at redo coronary artery bypass grafting. The ultrastructural features of cell death were analysed by electron microscopy. Typical features of necrosis, including focal areas of cytoplasmic oedema, plasmalemmal destruction and nuclear condensation with cytoplasmic organelle destruction, were observed throughout the intima and media. Features of apoptosis, including the presence of apoptotic bodies, were also identified in the hyperplastic intima and its adjacent media. Our observations suggest that both apoptosis and necrosis occur in non-atherosclerotic areas of stenotic aortocoronary saphenous vein bypass grafts.     

Oxidation and Endothelial Dysfunction Biomarkers of Atherosclerotic Plaque Instability. Studies of the Vascular Wall and Blood

The concentrations of LPO products (including those present in LDL), oxidative modification of proteins, paraoxonase activity, concentrations of antioxidants, lipid values and biomarkers of endothelial dysfunction were studied in the blood and coronary artery intima/media of male patients with coronary atherosclerosis without acute coronary syndrome. Blood levels of LDL oxidized apolipoproteins and lipoprotein (a) were higher, while the content of NO metabolites, sVCAM endothelial adhesion molecules, and LDL oxidation resistance were lower in men with mainly unstable atherosclerotic plaques in the coronary arteries in comparison with men with mainly stable plaques in the coronary arteries. Of these blood biomarkers, only NO metabolites, oxidized proteins, and sVCAM correlated with the presence of unstable atherosclerotic plaques. A significant correlation between the levels of biomarkers in the vascular wall and blood was detected only for LPO parameters.     

Histologic study of coronary, radial, ulnar, epigastric and internal thoracic arteries: application to coronary artery bypass grafts

The biometry and the histology of coronary, radial, ulnar, epigastric and internal thoracic arteries were studied in order to investigate the cause of their occlusions in coronary bypass grafts and to improve the results of these bypass grafts. These various arteries were removed from 40 anatomical specimens (27 males and 13 females). We found a correlation between the internal calibers of the ulnar and coronary arteries in males. Intimal changes and the presence of atheromatous plaque were observed in coronary, radial and ulnar arteries, but never in the internal thoracic artery. Like coronary arteries and their branches, radial, ulnar and epigastric arteries are muscular arteries and ageing results in thickening of the intima, which becomes fibrotic with migration of myocytes from the media and duplication of the internal elastic lamina. The media becomes fibrous, hypertrophic or atrophic. In contrast, the internal thoracic artery is an elastic artery, like the aorta. Ageing is characterized by loss, over a variable extent, of one or several elastic laminae of the media and more marked intimal thickening. Although anatomically, the caliber of radial, ulnar, and epigastric arteries remains adapted to that of coronary arteries, the long-term patency of radial, ulnar and epigastric arteries used as grafts is related to their histological characteristics.     

On the biology of saphenous vein grafts fitted with external synthetic sheaths and stents

Autologous saphenous vein is used as a conduit to bypass atherosclerotic lesions in both the coronary artery (coronary artery bypass graft surgery [CABG]) and in femoral arteries (infrainguinal bypass graft surgery [IIBS]). Despite the undoubted success and benefits of the procedures, graft failure occurs in 50% of cases within 10 years after surgery. A principal cause of late vein graft failure is intimal and medial hyperplasia and superimposed atherogenesis. Apart from lipid lowering therapy, no intervention has hitherto proved clinically effective in preventing late vein graft failure which clearly constitutes a major clinical and economic problem that needs to be urgently resolved. However, we have studied the effect of external synthetic stents and sheaths in pig models of vein into artery interposition grafting and found them to have a profound effect on vein graft remodelling and thickening. In this review, therefore, we will summarise the mechanisms underlying vein graft failure and how these stents influence these processes and the possible mechanisms involved as well as the application of these devices in preventing vein graft failure clinically.     

中青年冠状动脉粥样硬化患者颈动脉硬化的超声特征

目的 探讨中青年冠状动脉粥样硬化（CHD）患者颈动脉超声特征。方法 根据冠状动脉造影结果,将我院170例患者分为CHD组105例和对照组65例,再将CHD组分为单支病变组32例、双支病变组34例和三支病变组39例。所有患者年龄均在60岁以下,全部受检者行颈动脉彩色多普勒超声检查,运用统计软件分析所检测的颈动脉声像图参数。结果 中青年冠状动脉粥样硬化患者颈动脉斑块60%为中低回声斑块。CHD组颈动脉内中膜厚度、IMT增厚率及斑块检出率均高于对照组,三支病变组斑块检出率高于单支病变组,颈动脉IMT情况与     

牙周致病菌在动脉粥样硬化斑块中的检测

目的 检测冠状动脉粥样硬化斑块中的5种特异性牙周致病菌.方法 收集101例行冠状动脉搭桥手术患者的动脉粥样硬化斑块标本,采用Chelex-100法提取冠状动脉粥样硬化斑块中的DNA,并通过PCR分别检测动脉粥样硬化斑块中的牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg)、伴放线放线杆菌(Actinobacillus actinomycetemcomitans,Aa)、具核梭杆菌(Fusobacterium nucleatum,Fn)、中间普氏菌(Prevotella intermedia,Pi)、福赛斯坦纳菌(Tannerella forsythensis,Tf)5种牙周特异性致病菌.结果 101例患者动脉粥样硬化斑块中牙龈卟啉单胞菌(Pg)的检出率为31％,福赛斯坦纳菌(Tf)为42％,中间普氏菌(Pi)为26％,具核梭杆菌(Fn)为21％,伴放线放线杆菌(Aa)为23％.这几种细菌的PCR产物通过测序,结果与GenBank数据库中的序列进行比对同源性达99％～100％.结论 牙周致病菌在冠心病的发生、发展中可能发挥着一定作用,考虑慢性牙周炎与冠心病之间有一定的相关性.     

The modulation of smooth muscle cell phenotype is an early event in human aorto-coronary saphenous vein grafts

Summary The morphological changes in human vein grafts occurring in the first days after a coronary bypass operation (CBP) are rarely reported in the literature. Sections of aorto-coronary vein grafts from 11 patients who died during the first 10 days after a CBP were obtained at autopsy. The number of vein grafts per patient ranged from 1 to 4, yielding a total of 28 vein grafts. The early changes in the vein grafts have been studied by light microscopy, immunohistochemistry, transmission and scanning electron microscopy. The study demonstrates that soon after grafting, the vein wall is infiltrated by polymorphonuclear leucocytes (PMN). At 24 h the endothelium shows extensive desquamation. The massive migration of PMN through the venous wall occurs simultaneously with the endothelial damage. The circular layer of the media is severely damaged, resulting in a loss of smooth muscle cells (SMC). The remaining SMC in this layer show a change toward the synthetic phenotype and a reduced expression of α-smooth muscle actin. These early changes in the SMC function may initiate the process of fibrosis in the intima and the media of the vein grafts.     

The descending branch of the lateral circumflex femoral artery as an alternative conduit for coronary artery bypass grafting: Experience from an anatomical,radiological and histological study

The descending branch of the lateral circumflex femoral artery (DBLCFA) has been suggested as an option for use in coronary artery bypass grafting (CABG). Our aim was to combine radiological examination, surgical and anatomical preparation, and histological assessment of the DBLCFA to map its variability and to assess the benefits of this conduit in cardiac surgery. The pelvic and femoral arteries were examined by CT angiography (CTA) in 100 patients (aged 68.3 ± 9.3 years) to assess the variability of the DBLCFA. Anatomical dissections were performed on 20 cadavers. In 15 patients, an autologous DBLCFA was implanted during CABG. In 35 samples, possible atherosclerotic lesions were examined histologically. The length of the potential DBLCFA conduits measured by CTA was 9.3 ± 2.9 cm, without correlating with the length of the thigh. Anatomical variations that would prevent the DBLCFA from being used in CABG were found in 27 out of 100 patients. Except for focal thickening of the intima, eccentric hypertrophy of the intima was found in three out of 35 samples. No inflammatory infiltration, foam cells, atheroma, or calcifications were found histologically. The DBLCFA is not to be used routinely or in preference to other grafts of choice. However, owing to its moderate variability, sufficient length, caliber, and rare atherosclerosis, it can be used in the absence of other suitable grafts as an alternative conduit implanted as a composite Y‐graft end‐to‐side to the internal thoracic artery in patients without diabetic angiopathy, neuropathy or peripheral artery disease who are undergoing extensive or repeat coronary revascularization. Clin. Anat. 29:779–788, 2016. © 2016 Wiley Periodicals, Inc.     

血管内超声与64排螺旋CT分析冠状动脉斑块的对比研究

目的对冠状动脉病变患者进行血管内超声(IVUS)和64排螺旋CT(64MDCT)检查,评价两种检查手段在冠状动脉病变诊断中的应用价值。方法 24例临床怀疑或诊断为冠心病的患者接受冠状动脉64MDCT检查,并应用其工作站相关后处理技术对冠状动脉粥样斑块进行评估分析。一周内实施冠状动脉内IVUS检查,对冠状动脉病变进行定性和定量分析。结果分析病变血管52支,其中左主干24支,前降支21支,左回旋5支,右冠状动脉2支。IVUS显示有斑块病变的血管段为60段,64MDCT显示有斑块病变的血管样本57段,其中3段病变64MDCT诊断正常而IVUS显示为斑块早期病变。64MDCT对出现任何粥样硬化斑块节段诊断的敏感性为96%,特异性为94.7%。IVUS与64MDCT的管腔面积,外弹力膜面积、斑块面积的相关系数r分别为0.79、0.83、0.81。结论 IVUS能准确判断冠状动脉斑块的大小和性质。64MDCT作为非侵入性方法亦能显示管壁斑块的构成,判断病变的类型及程度,具有一定的敏感性和准确率。     

Inner layer infarction of the coronary artery wall due to coronary thrombosis

Cross sections of 112 coronary artery segments from 65 human hearts with coronary thromboses were investigated after postmortem coronary angiography. In almost all cases the inner layers of coronary artery walls adjacent to the obstructing thrombi or to parietal thrombi were infarcted. These infarctions followed nearly the same course as classical infarctions. From 13 hearts with segments occluded by thrombi but without atherosclerotic lesions, 19 specimens were found suitable for quantitative investigations. The 2 segments with the thinnest intima were lacking in inner layer infarctions. The other 17 specimens contained areas of inner layer necrosis of increasing diameter, depending on the thickness of the wall. In each case the media was completely preserved. The mean thickness of the noninfarcted wall tissue was 190+/-28 micro m. This noninfarcted wall tissue was supplied by vasa vasorum in the adventitia located at an average distance of approximately 40 micro m from the media. The knowledge of the supplying areas of the vasa vasorum could help us understand the pathogenesis of necroses in atherosclerotic plaques.     

Assessment of coronary artery bypass graft patency by multislice computed tomography

The recently developed multislice computed tomography (MSCT) is capable of rapid imaging of cardiac structures, including coronary arteries, during a single breath-hold. We evaluated coronary artery bypass graft (CABG) patency by comparing MSCT results to those of contrast angiography. MSCT and contrast angiography were performed in 39 patients (10 women, 29 men and mean age 60.0 +/- 7.8 years) with a total of 115 bypass grafts including 36 left internal mammary arteries, 4 right internal mammary arteries, 19 radial arteries, 2 gastroepiploic arteries and 54 vein grafts. Patients were investigated for an average of 14 +/- 27 months (range 1 - 108 months) after CABG surgery. Contrast angiography showed a patency rate of 87.0% (100/115). Ninety-nine of these 100 patent grafts by contrast angiography and 14 of the remaining 15 occluded grafts were correctly classified by MSCT (93.3% sensitivity and 99.0% specificity for bypass graft occlusion). The positive and negative predictive values for bypass graft occlusion were 93.3% and 99%, respectively, with an overall diagnostic accuracy of 98.3% (97.2% for left internal mammary artery, 100% for radial artery, 98.1% for vein graft and 100% for other grafts). In conclusion, MSCT is a useful and accurate diagnostic tool for the evaluation of bypass graft patency.     

Effect of angioplasty and grafting on porcine vascular nerves: a potential neurotropic role for endothelin-1

The most commonly performed procedure for treating coronary artery stenosis is percutaneous transluminal coronary angioplasty (PTCA) and, where the vessel lumen is severely narrowed, coronary artery bypass grafting (CABG). In PTCA, regions of atherosclerotic plaques are disrupted, and the vessel lumen increased by inflating a balloon catheter. In CABG an autologous saphenous vein into coronary artery interposition graft is performed in order to bypass occluded regions of epicardial coronary arteries. Both interventions cause varying degrees of vascular damage and the long-term efficacy of these procedures is limited by a high incidence of neointimal formation and subsequent vascular restenosis (Bach et al. 1994; Bryan & Angelini, 1994).
The endothelium-derived constrictor peptide, endothelin-1 (ET-1) (Yanagisawa et al. 1988), also possesses mitogenic activity on vascular smooth muscle cells (Hirata et al. 1989) and has been suggested as playing a role in atherosclerosis (Dashwood et al. 1993; Zeiher et al. 1994) and intimal hyperplasia (Dashwood et al. 1993; Douglas et al. 1994).     

Pathology of coronary artery bypass graft surgery.

Coronary artery bypass graft surgery has been available and widely successful for the symptomatic treatment of ischemic heart disease. Despite its widespread use, there is little information available on the pathological consequences of this procedure on the human heart. In this article, morphological consequences of coronary artery bypass graft surgery is reviewed. Intimal changes occurring within the vein graft itself consist predominately of fibrous initimal proliferation, which in some patients may progress to from an occlusive plaque. Most occlusions, however, occur at the coronary artery bypass graft anastomosis site and the mechanisms of occlusion include compression of the vascular lumen, thrombosis, and dissection of the coronary artery. Most graft failure occurs in the setting of too small a native coronary artery lumen. The myocardium is also at risk for alterations as a result of the bypass operation. Contraction band or reperfusion necrosis is the type of injury most commonly seen, and it appears to occur most often in the distribution of patent grafts. Accelerated atherosclerosis in vein grafts and the myocardial injury associated with revascularization require further detailed morphological studies, but these are important areas for pathological exploration since they bear on important and yet unanswered questions about coronary bypass surgery: can it in the long run perserve myocardium and prolong life?     

CT血管造影分析体外循环与非体外循环冠状动脉旁路移植后的桥血管通畅率

背景：近年来,非体外循环冠状动脉旁路移植后桥血管通畅率是否与传统的体外循环冠状动脉旁路移植相同存在争议。 目的：探讨体外循环与非体外循环冠状动脉旁路移植后桥血管时间通畅率的差异性。 方法：选取同一操作者行体外循环冠状动脉旁路移植患者100例,按其临床特征及桥血管病变危险因素匹配抽取非体外循环冠状动脉旁路移植患者137例。采用64排多螺旋CT血管造影分析冠脉搭桥后1个月,1年,2年,3年,4年的桥血管通畅情况。 结果与结论：共对641条桥血管进行评价,两组中左侧乳内动脉桥血管时间通畅率均高于大隐静脉桥,两组左侧乳内动脉桥和大隐静脉桥血管时间通畅率比较差异均无显著性意义。说明非体外循环与体外循环冠状动脉旁路移植后患者桥血管时间通畅率相似,对于某些适当的患者来说,非体外循环冠状动脉旁路移植不失为一个良好的选择。     

Mechanical stretching of human saphenous vein grafts induces expression and activation of matrix-degrading enzymes associated with vascular tissue injury and repair.

After coronary artery bypass surgery, saphenous vein graft occlusion occurs through tissue remodeling. Although a likely trigger, the role of preparative mechanical injury incurred by the graft is not yet understood. We studied the early effects of simple mechanical injury on human saphenous vein grafts by exposing them to longitudinal stretch, a deformation which potentially occurs during surgery. We then maintained ex vivo for up to 7 days matched pairs of experimentally stretched and nonstretched (control) vein segments and examined the expression and activation of matrix metalloproteinases (MMPs) and integrin alphav, molecules implicated in vascular remodeling. At peak expression on day 3, stretched vein secreted 177 +/- 16% active MMP-2 (P < 0.01), 161 +/- 36% (P < 0.05) pro-MMP-9, and contained 206 +/- 18% (P < 0.01) alphav, a receptor for active MMP-2, compared to control. In situ gelatinase activity was present in the intima and adventitia of stretched veins, but not of control, and correlated spatially with expression of alphav. Stretch also increased severalfold cell proliferation (1.27 +/- 0.4 vs. 0.23 +/- 0.05% in control, P < 0.05), as assessed by bromodeoxyuridine incorporation. Furthermore, we found that cell proliferation colocalized with gelatinase activity and alphav in the adventitia. Our results show that a single longitudinal stretch of vein grafts produces significant changes in the expression and activation of key molecules in vascular remodeling. We also found support for the notion that the adventitial layer contributes to vein graft remodeling.     

Foam cell replication and smooth muscle cell apoptosis in human saphenous vein grafts

Occlusion of saphenous vein grafts is a major problem after coronary artery bypass grafting. Segments of occluded and suboccluded implanted aortocoronary grafts were obtained during re-intervention bypass grafting in 47 patients yielding a total of 80 vein grafts. The grafts were studied by immunohistochemistry for smooth muscle cells (ÉL-SMC actin), macrophages (HAM56), cell replication (PCNA, Ki-67) and transmission and scanning electronmicroscopy (TEM, SEM). In 81% of the examined grafts the (sub)occlusion was due to a myo-intimal thickening and an associated luminal accumulation of foam cells and mural thrombi. The foam cells were constantly found at the luminal site of the myo-intimal thickening and within the luminal part of adherent thrombi. Transmission electronmicroscopy demonstrated phagocytosis of platelets and platelet fragments by the foam cells. A significant fraction of the foam cells demonstrated nuclear immunoreactivity for Ki-67 and PCNA. The myo-intimal thickening of the vein grafts was composed of smooth muscle cells lying in a fibrous tissue matrix. The smooth muscle cells were surrounded by prominent basal lamina and showed ultrastructural features of apoptosis. Our results support the hypothesis that phagocytosis of lipid rich platelets by monocytes set up a mechanism for foam cell formation and replication in human saphenous vein grafts. The transformation of a smooth muscle cell rich myo-intimal thickening towards a fibrous, cell poor intimal thickening could be induced by progressive smooth muscle cell loss through apoptosis.     

Histopathological Study of Aorto-Coronary Bypass Grafts With Special Reference to Fibrin Deposits on Grafted Saphenous Veins

A histopathological study was performed on 36 patients (60 grafts) who had undergone aorto-coronary bypass graft (ACBG) surgery 0 to 99 months prior to death. The following pathologic changes were found: 1) The thickness of diffuse intimal proliferation in the ACBG progressed with time from graft surgery to death. 2) The media became atrophic and the adventitia was increased slightly in thickness. 3) Fibrin deposits were found in 20 patients on/in the intimal thickenings of the vein graft walls and 7 patients showed incorporated fibrin in the thickened intima even one month after surgery. 4) Atherosclerosis, identified as intimal foam cell accumulation or frank plaques, was seen in only 3 patients 4 years after surgery. Fi-brointimal proliferation occurred with relatively greater frequency in patients with fibrin deposits (P< 0.001). Although it is well known that mural thrombi in vein grafts manifest fibrointimal proliferation, our results suggest that fibrin deposits might be responsible for intimal thickening even one month after graft surgery. Acta Pathol Jpn 39: 425 432, 1989.