COAGULATION HOMEOSTASIS & CORONARY ARTERY THROMBOSIS

对急性心肌梗死后患者的研究证明 对了解心肌损伤的反应很有价值。 然而，这样的研究还无法提供信息 关于血栓形成，因为血栓形成明显早于血栓形成 学习的时间。术后有促凝血活性的证据 心肌梗死的发生是不可靠的反映 因果关系的易感状态尚不清楚 杰出的。已经开发了一些模型，例如运动或 起搏引起的心绞痛，虽然这些让我们洞察到 他们还没有证明心脏对缺氧和缺血的反应 对血栓形成的研究很有用。我们假设 凝血酶和纤溶酶作用的平衡是主要的最终结果 血栓形成的决定因素。过度的凝血酶作用会产生 血栓形成，过量的纤溶酶作用可防止血栓形成。介于 这两个极端的一过性血栓可能会发展并随后 Lyse，给出不稳定性心绞痛和自发性心绞痛的证候 缺血症。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，它们的设计是基于 关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 自发性脑缺血。通过同步的Holter记录 在心电图中，我们会把缺血的发生与血浆联系起来。 纤维蛋白多肽和血小板蛋白水平可作为 凝血、纤维蛋白溶解和血小板活化。一种类似的 在对溶栓后患者的研究中将采取这种方法。 这一组有很高的再闭合发生率，通常是 心肌梗塞，冠状动脉溶栓成功后不久。我们 还将研究接受溶栓治疗的患者 确定我们所拥有的凝血酶活性的来源 之前发现的。凝血和血小板活化与患者的关系 接受冠状动脉血管成形术将作为一种模型研究 斑块破裂与急性心肌梗死相关。新的 将建立对因子IX的激活肽的检测方法 和X，以及凝血酶原片段F1+2。这些将用于 探测凝固级联中的早期事件。一位高度 灵敏、特异的稳定同位素稀释法 为11-脱氢血栓素B2开发的。这将允许 准确、准确地测定血栓素A2的产生， 它不会受到体外血小板激活的影响。

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.