COAGULATION HOMEOSTASIS & CORONARY ARTERY THROMBOSIS

对急性心肌梗死患者的研究已经证明， 对了解心肌损伤的反应有价值。 然而，这些研究未能提供信息， 血栓形成，因为血栓形成明显先于 学习的时间。 促凝血活性的证据， 心肌梗死的发生是不可靠的， 由于因果关系不能清楚地 杰出的 已经开发了模型，例如锻炼或 起搏引起的心绞痛，虽然这些已经让我们了解到 心脏对缺氧和缺血的反应， 用于血栓形成的研究。 我们假设 凝血酶和纤溶酶作用的平衡是 血栓形成的决定因素。 过量的凝血酶作用产生 血栓形成，过量的纤溶酶作用防止血栓形成。 之间 这两个极端的短暂血栓可能会发展， 溶解，给出不稳定型心绞痛和自发性 缺血 我们建议的研究旨在获得以下数据： 实际血栓形成之前的事件，其设计基于 我们在这方面进行研究的经验。 我们建议 对不稳定型心绞痛患者进行详细的系列研究， 自发性缺血 通过同步霍尔特记录 我们将把缺血发作与血浆 纤维蛋白肽和血小板蛋白水平，作为 凝血、纤溶和血小板活化。 类似的 将在溶栓后患者的研究中采用这种方法。 这一组的再闭塞发生率很高， 在成功的冠状动脉溶栓后不久发生梗死。 我们 还将研究接受溶栓治疗的患者， 确定凝血酶活性的来源， 患者的凝血和血小板活化 进行冠状动脉成形术将作为模型进行研究， 斑块破裂与急性心肌梗死相关。 新 将开发用于因子IX的活化肽的测定法 和X，以及凝血酶原片段F1+2。 这些将用于 探测凝血级联中的早期事件。 一个高度 灵敏度和特异性稳定同位素稀释分析将是 针对11-羟血栓素B2开发的。 这将允许 准确、精密地测定血栓素A2的产生， 其将不受离体血小板活化的影响。

Studies of patients after acute myocardial infarction have proved valuable in understanding the response to myocardial injury. However, such studies have not been able to provide information on thrombogenesis, since thrombus formation clearly antecedes the time of study. Evidence of procoagulant activity after myocardial infarction has occurred is unreliable as a reflection of the predisposing state since cause and effect cannot be clearly distinguished. Models have been developed, such as exercise or pacing induced angina, and while these have given insight into cardiac response to hypoxia and ischemia they have not proved useful for studies of thrombogenesis. We hypothesize that balance of thrombin and plasmin action is the major final determinant of thrombosis. Excess thrombin action produces thrombosis, excess plasmin action prevents thrombosis. Between the two extremes transient thrombi may develop and subsequently lyse, giving the syndromes of unstable angina and spontaneous ischemia. The studies we propose are aimed at obtaining data on the events preceding actual thrombosis, and their design is based on our experience of making studies in this area. We propose to make detailed serial studies of patients with unstable angina and with spontaneous ischemia. By the simultaneous Holter recording of the ECG we will relate the onset of ischemia to the plasma levels of fibrinopeptides and platelet proteins, as markers of coagulation, fibroinolysis and platelet activation. A similar approach will be taken in studies of patients post thrombolysis. This group has a high incidence of reocclusion, often with infarction, shortly after successful coronary thrombolysis. We will also study patients undergoing thrombolytic therapy to determine the origin of the thrombin activity which we have previously found. Coagulation and platelet activation in patients undergoing coronary angioplasty will be studied as a model of the plaque rupture associated with acute myocardial infarction. New assays will be developed for the activation peptides of factors IX and X, and for prothrombin fragment F1+2. These will be used to probe earlier events in the coagulation cascade. A highly sensitive and specific stable-isotope dilution assay will be developed for 11-dehydro thromboxane B2. This will allow the accurate and precise determination thromboxane A2 production, which will not be affected by ex vivo platelet activation.