MYOCARDIAL CELL STRUCTURE IN SIMULATED ISCHEMIA

模拟缺血中的心肌细胞结构

• 批准号: 3448469
• 负责人: EDORIS ANN LEFURGEY
• 金额: $ 5.63万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1985-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3448469
• 关键词: acidosis; cardiotonic agents; cell morphology; cellular pathology; chlorpromazine; heart pharmacology; mitochondria; myocardial infarction; myocardial ischemia /hypoxia; myofibrils; nifedipine; quinidine; sarcoplasmic reticulum; scanning tunneling microscopy; tissue /cell culture

Extensive studies on the subcellular pathophysiology of ischemia in vivo and in vitro in diverse tissues have documented morphological and functional events leading to irreversible cell damage, events which may be related to alterations in the transport of diffusible ions across cell or organelle membranes. The proposed experiments will test the hypothesis that translocation and redistribution of physiologically important ions occur at the subcellular level which parallel loss of ultrastructural integrity during selected conditions simulating the in vivo ischemic process. The experimental model to be used--embryonic chick myocardial cells in culture--offers the unique ability to study, singly or in combination, factors which contribute to ischemic injury, such as active transport inhibition, hypoxia, metabolic deprivation, and acidosis. Techniques of analytical transmission electron microscopy including cryopreparation and energy dispersive X-ray spectroscopy will facilitate location and quantitation of the ions Na plus, K plus, Ca++, Mg++, and Pi within subcellular regions 10 to 20 nM in diameter. The ionic composition, ultrastructural integrity, spatial morphology and morphometry of myocardial cells will be monitored as the preparations are a) acutely or chronically exposed to ischemic conditions, and b) challenged to adapt and/or to recover following either acute or long term exposure. The ability to study in isolation individual morphological, physiological, and biochemical factors contributing to the ischemic process is unique to the cultured heart cell model. Coupled with electron probe localization and quantitation of elements within subcellular compartments, the model will enable the assessment of the role of ionic shifts in irreversible cell damage, particularly the role which structural damage may play in altered ionic compartmentation. The importance of determining the mechanisms responsible for cell injury lies in the potential for manipulation of these events, and subsequently the development of appropriate clinical interventions for control and prevention of ischemia-related diseases such as myocardial infarction.

在体脑缺血亚细胞病理生理的广泛研究 在体外不同的组织中记录了形态和 导致不可逆细胞损害的功能事件，可能是 与可扩散离子在细胞或细胞间的运输变化有关的 细胞器膜。拟议中的实验将检验这一假设。 生理上重要离子的移位和重新分配 发生在亚细胞水平，与超微结构的损失平行 模拟体内缺血的选定条件下的完整性 进程。拟用的实验模型--鸡胚心肌 培养中的细胞--提供独特的研究能力，无论是单独研究还是在 组合，导致缺血性损伤的因素，如活跃的 运输抑制、缺氧、代谢剥夺和酸中毒。 分析电子显微镜技术包括 冷冻修复和能量色散X射线光谱分析将促进 离子Na~+、K~+、Ca~(++)、Mg~(++)和PI的定位和定量 在直径10到20纳米的亚细胞区内。离子组成， 心肌超微结构完整性、空间形态和形态计量学研究 细胞将被监测，因为准备是a)急性或慢性 暴露在缺血条件下，以及b)面临适应和/或 在急性或长期暴露后恢复。学习的能力 孤立的个体形态、生理和生化 促进缺血过程的因素是培养的人所独有的 心脏细胞模型。再加上电子探针定位和 亚细胞隔间内元素的定量，模型将 能够评估离子位移在不可逆电池中的作用 损害，特别是结构损害在改变中可能起到的作用 离子隔间。确定机制的重要性 造成细胞损伤的原因在于它们的潜在操纵性 事件，以及随后适当的临床发展 控制和预防与缺血有关的疾病的干预措施 作为心肌梗死。