SCOR IN CORONARY AND VASCULAR DISEASES

冠状动脉和血管疾病中的 SCOR

• 批准号: 3106515
• 负责人: JOHN JR ROSS
• 金额: $ 143.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3106515
• 关键词: heart disorder diagnosis; myocardial ischemia /hypoxia

The proposed Specialized Center of Research on Coronary Heart Disease is a broad laboratory and clinical research effort focused on the general goal of elucidating mechanisms of myocardial cell injury, adaptive responses to ischemia and infarction over time, and approaches for modifying and reversing the injurious effects of coronary heart disease. Mechanisms of ischemic cell injury will be explored by studying beta-adrenergic receptor properties and post-receptor mechanisms, G protein expression studied being by cDNA probes; Na+ channel gene expression in ischemia and hypertrophied myocardium, with in situ hybridization techniques to assess their distribution; heat shock protein (HSP) expression, and its potential protective effect and appearance of other mRNAs in ischemic and infarcted tissue; the injurious effects of leukocytes and mechanisms by which their activation can be studied in microcirculatory and intact animal models, with clinical studies on the predictive value of the activated leukocyte pool size; of the pre- and post-synaptic alpha1 and alpha2 receptor activation and blockade on the coronary vessels and myocardium, particularly in exercise-induced ischemia. Studies on adaptive responses will include mechanisms involved in the recovery of left ventricular function after experimental coronary occlusion and reperfusion, in particular the role of stunning and subsequent hypertrophy studied by mRNA markers of contractile protein synthesis; changes in the beta receptor life cycle and Na+ channel late after coronary occlusion with reperfusion; the mechanical effects of infarction and later scarring on finite left ventricular strains; regional stress effects on myocardial blood flow, and alterations in the collagen matrix and applications of NMR spectroscopy, including a chronically instrumented animal model allowing long and applications of NMR spectroscopy, including a chronically instrumented animal model allowing long term 31P spectroscopy studies, and advanced mechanisms to investigate other metabolites. Approaches for modifying or reversing effects of coronary heart disease will include experimental studies on improving the recovery of regional myocardial function after reperfusion; investigations on the effects of lowering the serum cholesterol on functional coronary reactivity and anatomy using digital imaging techniques in patients with coronary heart disease; the role of coronary angiography following acute myocardial infarction, and identification of high risk patients with depressed cardiac function who have dysfunctional but viable zones using positron emission tomographic imaging (PET). In an expanded UCSD SCOR Postinfarction Database, prospective studies across countries (United States, Canada, and Sweden) with widely differing management strategies, will use descriptive and analytic studies to examine outcomes and cost-effectivenesses of various diagnostic and therapeutic approaches in patient substrata, using a cost- effectivenesses of various diagnostic and therapeutic approaches in patient substrata, using a multivariate risk stratification scheme. This interdepartmental program will bring the disciplines of molecular biology, pharmacology, cardiovascular physiology, bioengineering, epidemiology, pathology and cardiology, together with their associated technologies, to bear on the solution of these significant problems in the pathogenesis and therapy of coronary heart disease.

拟议中的冠心病专门研究中心是一个 广泛的实验室和临床研究工作集中在总体目标 阐明心肌细胞损伤的机制， 缺血和梗塞的方法，以及改变和 逆转冠心病的有害影响。 机制 通过研究β-肾上腺素能受体将探索缺血性细胞损伤 性质和后受体机制，G蛋白表达研究正在进行 用cDNA探针检测缺血和肥厚心肌Na+通道基因表达 心肌，原位杂交技术，以评估其 分布;热休克蛋白（HSP）表达，及其潜力 保护作用和其他mRNAs在缺血和梗死中的表现 组织;白细胞的损伤作用及其机制， 可以在微循环和完整动物模型中研究活化， 与临床研究的预测价值的活化白细胞 突触前和突触后α 1和α 2受体的池大小 激活和阻断冠状血管和心肌， 特别是在运动诱发的局部缺血中。 适应性反应研究 将包括参与左心室恢复的机制， 实验性冠状动脉闭塞和再灌注后的功能， 特别是通过mRNA研究的顿抑和随后的肥大的作用 收缩蛋白合成的标志物; β受体寿命的变化 冠状动脉闭塞再灌注后晚期心肌细胞周期和Na+通道的变化; 梗死和后期瘢痕形成对有限左心室的机械影响 心室应变;局部应力对心肌血流的影响，以及 胶原蛋白基质的改变和NMR光谱的应用， 包括长期使用仪器的动物模型， 核磁共振光谱学的应用，包括长期仪器化的 动物模型允许长期的31 P光谱研究，和先进的 研究其他代谢物的机制。 修改或 逆转冠心病的影响将包括实验性的 促进术后局部心肌功能恢复的研究 再灌注;研究降低血清 胆固醇对功能性冠状动脉反应性和解剖学的影响 冠状动脉造影技术在冠心病患者中的作用 急性心肌梗死后的冠状动脉造影，以及 识别患有心功能低下的高危患者， 使用正电子发射断层扫描， 成像（PET）。 在扩展的UCSD SCOR梗死后数据库中， 跨国家（美国、加拿大和瑞典）的前瞻性研究 不同的管理策略，将使用描述性和 分析研究，审查各种方案的成果和成本效益， 诊断和治疗方法在病人的基层，使用成本- 各种诊断和治疗方法在患者中的有效性 使用多变量风险分层方案。 这 跨部门计划将带来分子生物学学科， 药理学，心血管生理学，生物工程学，流行病学， 病理学和心脏病学及其相关技术， 关系到发病机制中这些重大问题的解决， 冠心病的治疗。