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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1992年第1期667卷 204-223页

作者： FALK, E ODENSE UNIV INST FORENS MED DK-5000 ODENSE DENMARK

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ADJUNCTIVE THERAPY WITH LOW-MOLECULAR-WEIGHT HEPARIN WITH RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR CAUSES SUSTAINED REFLOW IN CANINE CORONARY-THROMBOSIS

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AMERICAN HEART JOURNAL 1992年第2期124卷 280-288页

作者： NICOLINI, FA NICHOLS, WW SALDEEN, TGP KHAN, S MEHTA, JL UNIV FLORIDA COLL MED DEPT MED BOX 100277 GAINESVILLE FL 32610 USA UNIV FLORIDA COLL MED DEPT PATHOL GAINESVILLE FL 32610 USA VET AFFAIRS MED CTR DIV CARDIOL GAINESVILLE FL USA UNIV UPPSALA DEPT FORENS MED S-75105 UPPSALA SWEDEN

Rethrombosis of the infarct-related artery after pharmacologic thrombolysis is a major limitation of the thrombolytic therapy. Platelet and fibrin deposition in the coronary artery after recombinant tissue-type plasminogen activator (rTPA) may play a leading role in reformation of thrombus. Therefore we examined the effect of low molecular weight heparin (LMWH) as adjunctive treatment with rTPA in a dog model of electrically induced intracoronary thrombus. Fourteen dogs, in which a stable coronary thrombus was induced with delivery of 100-mu-A of anodal direct current, were randomly given an intravenous bolus of LMWH, 75 IU/kg (n = 6), or saline (n = 8), followed by intravenous rTPA, 1 mg/kg over 20 minutes. LMWH (75 IU/kg) or saline was continuously infused over 90 minutes after rTPA-induced thrombolysis. Reperfusion occurred at 29 +/- 7 minutes in six of eight dogs receiving rTPA plus saline (reperfusion rate 75%), while reperfusion occurred at 18 +/- 3 minutes in all six dogs receiving rTPA plus LMWH (both p = NS versus rTPA plus saline group). Coronary reocclusion occurred in 83% of dogs given rTPA plus saline, but only in one dog (17%) given rTPA plus LMWH (p < 0.05). Magnitude of reflow at 60 minutes of reperfusion was higher in the rTPA plus LMWH group than in the rTPA plus saline group (51 +/- 14 ml/min versus 10 +/- 9 ml/min;p < 0.05). As expected, partial thromboplastin time was greater in rTPA plus LMWH than in rTPA plus saline-treated animals. Scanning electron microscopy (SEM) of coronary arteries showed a totally occlusive thrombus and intense platelet-fibrin deposition in dogs treated with rTPA plus saline. SEM showed a residual partially occlusive thrombus with qualitatively less platelet-fibrin deposition in dogs receiving rTPA plus LMWH. Thus adjunctive therapy with LMWH results in sustained reflow;however, the coronary artery continues to show residual thrombus and platelet-fibrin deposition.

关键词：冠状动脉循环/药物作用冠状动脉血栓形成/药物疗法冠状动脉血栓形成/病理学冠状血管/超微结构肝素低分子量/治疗应用显微镜检查电子扫描重组蛋白质类/治疗应用复发血栓溶解疗法组织型纤溶酶原激活物/治疗应用动物狗

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Evidence that high-density lipoprotein cholesterol is an independent predictor of acute platelet-dependent thrombus formation

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第9期84卷 1011-1017页

作者： Naqvi, TZ Shah, PK Ivey, PA Molloy, MD Thomas, AM Panicker, S Ahmed, A Cercek, B Kaul, S Cedars Sinai Med Ctr Div Cardiol Burns & Allen Res Inst Dept Med Los Angeles CA 90048 USA Cedars Sinai Med Ctr Vasc Physiol & Thrombosis Res Lab Atherosclerosis Res Ctr Los Angeles CA 90048 USA Univ Calif Los Angeles Sch Med Los Angeles CA 90024 USA Specialty Labs Inc Santa Monica CA USA

Plasma total and low-density lipoprotein (LDL) cholesterol are established risk factors for atherosclerotic vascular disease and may also contribute to a prothrombotic risk via enhanced platelet reactivity, This study examines whether high-density lipoprotein (HDL) cholesterol, which is inversely correlated with coronary artery disease, is associated with a reduced thrombogenic potential. Platelet thrombus formation was evaluated by exposing porcine aortic media placed in Badimon perfusion chambers to flowing nonanticoagulated venous blood for 5 minutes at a shear rate of 1,000 s(-1). Forty-five subjects, 23 normal (LDL 104 +/- 31, HDL 50 + /- 15 mg/dl) and 22 hypercholesterolemic (LDL 181 +/- 45, HDL 41 + 10 mg/dl) patients without coronary artery disease were studied. Platelet aggregation and CD62 antigen expression, and assay for circulating prothrom botic factors were also performed. In univariate analysis platelet thrombus formation correlated with weight (r = 0.33, p = 0.03), diastolic blood pressure (r = 0.39, p = 0.01), HDL cholesterol (r -0.45, p = 0.003), total/HDL cholesterol (r = 0.43, p = 0.004) and LDL/HDL (r = 0.38, p = 0.01) ratios, and platelet CD62 expression (r = 0.41, p = 0.02), In multiple regression analysis only HDL cholesterol showed significant correlation with platelet thrombus formation (p = 0.03), Platelet aggregation and circulating prothrombotic factors did not correlate with platelet thrombus formation. A comparison between normal and hypercholesterolemic subjects revealed enhanced thrombus area (0.026 +/- 0.20 vs 0.045 +/- 0.039 mm(2)/mm;p = 0.04), resting CD62 expression (6 + 7% vs 15 +/- 10% positive platelets, p = 0.02), and platelet aggregation (16.7 + 5.2 vs 21.7 +/- 6.7 ohms, p = 0.04) in hypercholesterolemic subjects. Our results demonstrate that HDL cholesterol is ct significant independent predictor of ex vivo platelet thrombus formation. (C) 1999 by Excerpta Medica, Inc.

关键词：胆固醇 HDL/血液胆固醇 LDL/血液冠状动脉血栓形成/血液冠状动脉血栓形成/病理学高胆固醇血症/血液高胆固醇血症/病理学显微镜检查电子扫描模型心血管血小板聚集/生理学凝血酶原/代谢危险因素猪血管中膜/代谢血管中膜/病理学成年人动物女(雌)性人类男(雄)性中年人

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Vascular repair after balloon overstretch injury in porcine model effects of intracoronary radiation

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第4期36卷 1389-1395页

作者： Cottin, Y Kollum, M Chan, R Bhargava, B Vodovotz, Y Waksman, R Washington Hosp Ctr Inst Cardiovasc Res Vasc Brachytherapy Inst Washington DC 20010 USA Washington Hosp Ctr Dept Radiat Oncol Washington DC 20010 USA

OBJECTIVES The purpose of this study was to evaluate the effect of IR on thrombus formation and dissection repair following overstretch balloon injury in porcine coronary arteries. BACKGROUND Exposure of blood to the injured arterial wall after percutaneous transluminal coronary angioplasty (PTCA) induces thrombus formation and inflammation in the dissection plane. Neointima formation is related to smooth muscle cell (SMC) proliferation and migration into the preformed thrombus. Intracoronary radiation (IR) with doses of 10 to 25 Gy using either beta or gamma emitters can prevent neointima accumulation by reducing SMC proliferation. However, there are some indications that IR may delay the process of dissection repair after PTCA. The purpose of this study was to evaluate the effect of IR on thrombus formation and dissection repair after overstretch balloon injury in porcine coronary arteries. METHODS Forty porcine coronaries were injured by balloon overstretch followed by either 0 or 18 Gy of Y-90 prescribed to 1.2 mm from the balloon center. The animals were euthanized 14 days after treatment, and intimal area (IA) and IA corrected for medial fracture length (IA/FL) were quantified by digital image analysis. Dissections were quantified by tracing the length, thickness and area behind the dissection flap. The rate of dissections was calculated for each group. Thrombi were identified and designated as intraluminal thrombus or thrombus within dissection planes (mural thrombus), and area measurements were obtained. RESULTS The irradiated group showed a significant reduction of IA/FL (0.55 +/- 0.29 vs. 0.05 +/- 0.09;p < 0.001). No difference was observed in the rare of dissection between control and irradiated arteries (77% vs. 88%, respectively). The control group showed a smaller dissection area (0.19 +/- 0.28 mm(2) vs. 0.32 +/- 0.29 mm;p < 0.05) with smaller mural thrombi (0.03 +/- 0.01 mm(2) vs. 0.29 +/- 0.30 mm2;p < 0.001). A strong correlation between dissection a

关键词：血管成形术气囊冠状动脉/副作用近距离放射疗法/方法冠状动脉血栓形成/病因学冠状动脉血栓形成/病理学冠状动脉血栓形成/放射疗法冠状血管/损伤冠状血管/病理学冠状血管/辐射效应疾病模型动物猪血管内膜/病理学血管内膜/辐射效应动物

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Tissue characteristics of restenosis after percutaneous transluminal coronary angioplasty in diabetic patients

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第4期34卷 1045-1049页

作者： Moreno, PR Fallon, JT Murcia, AM Leon, MN Simosa, H Fuster, V Palacios, IF Univ Kentucky Gill Heart Inst Lexington KY USA Mt Sinai Sch Med Dept Pathol New York NY USA Harvard Univ Sch Med Massachusetts Gen Hosp Cardiac Unit Boston MA 02114 USA Cardiovasc Inst New York NY USA

The purposes of this study were to analyze coronary specimens from patients with diabetes mellitus (DM) and to compare them with specimens from patients without DM. BACKGROUND Diabetes mellitus is associated with an increased incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Increased hypercellular smooth muscle cell proliferation with exaggerated intimal hyperplasia formation may be responsible for this predisposition. METHODS Eighteen coronary atherectomy specimens with restenosis after PTCA from patients with DM were compared with 18 coronary atherectomy specimens with restenosis after PTCA from patients without DMI. Total and segmental areas were quantified on trichrome-stained tissue of hypercellular tissue, collagen-rich sclerotic tissue, atheroma and thrombus. Demographic and angiographic data were similar in both groups. RESULTS The percentage of total plaque area composed of hypercellular tissue was lower in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (19 +/- 6% vs. 44 +/- 5%;p = 0.003). The percentage of collagen-rich sclerotic tissue area was larger in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (77 +/- 9% vs. 53 +/- 4%;p = 0.004). The percentages of atheroma and thrombus were similar in both groups. CONLUSIONS Intimal hypercellular tissue content is reduced in restenotic tissue from patients with DM. Collagen-rich sclerotic content is increased in restenotic lesions from patients with DM. These results suggest an accelerated fibrotic rather than a proliferative response in diabetic lesions from patients with restenosis after PTCA.. (J Am Cell Cardiol 1999;34:1045-9) (C) 1999 by the American College of Cardiology.

关键词：血管成形术气囊冠状动脉斑块切除术冠状动脉细胞分裂/生理学冠状动脉疾病/病理学冠状动脉疾病/治疗冠状动脉血栓形成/病理学糖尿病血管病变/病理学糖尿病血管病变/治疗纤维肌性发育不良/病理学肌平滑血管/病理学复发再治疗危险因素血管内膜/病理学老年人女(雌)性人类男(雄)性中年人

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Detecting and differentiating white from red coronary thrombus by angiography in angina pectoris and in acute myocardial infarction

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第1期83卷 94-+页

作者： Abela, GS Eisenberg, JD Mittleman, MA Nesto, RW Leeman, D Zarich, S Waxman, S Prieto, AR Manzo, KS Michigan State Univ Dept Med Cardiol Clin Ctr B208 E Lansing MI 48824 USA Harvard Univ Sch Med Deaconess Hosp Dept MedDiv Cardiol Boston MA USA

To determine the ability to detect thrombus by angiography, angioscopy was performed before angiography in patients undergoing interventional procedures and the data collected in a blinded fashion. These data demonstrated that the sensitivity of angiography to detect white thrombus was 50% and the specificity was 95%, whereas the sensitivity and specificity to detect red thrombus was 100%, respectively;the positive and negative predictive value of detecting thrombus in general was 89% and 83%, respectively.

关键词：心绞痛/病因学心绞痛/病理学心绞痛/放射摄影术血管镜检查冠状血管造影术冠状动脉血栓形成/并发症冠状动脉血栓形成/病理学冠状动脉血栓形成/放射摄影术冠状血管/病理学诊断鉴别心肌梗死/病因学心肌梗死/病理学心肌梗死/放射摄影术试验预期值敏感性与特异性老年人女(雌)性人类男(雄)性中年人

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Plaque disruption and thrombosis. Potential role of inflammation and infection

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Cardiology Clinics 1999年第2期17卷 271-281页

作者： Shah, P.K. Division of Cardiology Atherosclerosis Research Center Cedars-Sinai Medical Center Los Angeles CA 90048 United States

Considerable data from in vitro and in vivo studies of vascular biology, together with indirect evidence from clinical trials of lipid-lowering or modifying and lifestyle or risk factor modifying interventions, provide strong support for the concept that disruption of atherosclerotic plaque and subsequent thrombosis is a key precipitant of potentially lethal, acute coronary syndromes. Certain characteristics of plaques, including the size and composition of the lipid core, the structure and composition of the fibrous cap, and the presence of a local inflammatory process, predispose the plaque to disruption. Stresses resulting from biomechanical and hemodynamic forces acting on plaques may then trigger disruption, releasing the thrombogenic contents of the lipid core. Alterations in endothelial function may also contribute to vulnerability of plaque rupture and thrombosis. Therefore, interventions aimed at decreasing plaque vulnerability to disruption all based on the concept of plaque stabilization may reduce the risk of acute coronary syndromes. Although not yet rigorously validated in humans, plaque stabilization may prove to be an important clinical strategy for preventing the lethal consequences of coronary atherosclerosis.

关键词：细胞凋亡生物力学冠状动脉血栓形成/病理学冠状动脉血栓形成/病理生理学炎症/病理生理学金属内肽酶类/分析破裂自发性应力物理人类

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Importance of microembolization and inflammation in atherosclerotic heart disease

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AMERICAN HEART JOURNAL 2000年第6期140卷 S90-S102页

作者： Yamada, DM Topol, EJ Cleveland Clin Fdn Dept Cardiol Cleveland OH 44195 USA

Considerable evidence now exists that inflammation is a central component of events that initiate and propagate on acute coronary syndrome. This process evokes the potential for embolization, which occurs more often than previously suspected, and imparts poor cardiovascular prognosis. Recent development of techniques to detect inflammation and embolization represents an important advance. In addition, therapies that diminish occurrence of these phenomena such as aspirin, statins, angiotensin converting enzyme (ACE) inhibitors, and IIb/IIIa receptor antagonists have been shown to improve outlook.

关键词：生物学标记/血液 C反应蛋白质/代谢冠状动脉血栓形成/血液冠状动脉血栓形成/并发症冠状动脉血栓形成/病理学炎症/血液炎症/并发症炎症/病理学白细胞介素6/血液预后疾病严重程度指数血栓栓塞/血液血栓栓塞/并发症血栓栓塞/病理学肌钙蛋白/血液人类

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