IN VITRO MODEL OF PRECONDITIONING WITH ISOLATED MYOCYTES

分离的心肌细胞预处理的体外模型

• 批准号: 2228852
• 负责人: CHARLES E GANOTE
• 金额: $ 8.2万
• 依托单位: EAST TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2228852
• 关键词: adenosine; chemoprevention; conditioning; deoxyglucose; disease /disorder model; glycolysis; guinea pigs; heart cell; high energy particle; laboratory rabbit; myocardial ischemia /hypoxia; pertussis toxin; phosphatase inhibitor; phosphorylation; protein kinase C; species difference; tissue /cell culture

The objectives are to determine the mechanisms by which preconditioning protect from ischemic injury. Preconditioning refers to a period of resistance to ischemic injury, that can be induced by temporary ischemic, hypoxia or adenosine A1 receptors, prior to a period of sustained ischemic. Neither at the natural trigger, the target tissue (nerve, vascular, myocyte or interstitial), nor the mechanisms responsible for in situ preconditioning have been established. To date, preconditioning has only been shown to occur in intact hearts or animals. A new observation is that isolated adult rabbit cardiomyocytes can be endogenously preconditioned against subsequent ischemia, by a brief, substrate-free, oxygenated incubation period. This preconditioning conferes a high degree of protection (1-2 hour delay in death) from subsequent ischemia. In vitro- preconditioning mechanisms do not appear related to energy utilization/production, or to catacholamines. This proposal, focuses on characterization of this new model, as a basis for future studies of endogenous cellular mechanisms of preconditioning. The aims are to determine; A. the relations between protection and high energy phosphate levels; B. if the trigger, and protection are/are not analogous to that in intact hearts; C. if preconditioning decays during a post incubation period prior to ischemia; D. determine if the pathways of preconditioning, and protein phosphatase inhibitors converge to a common PKC-related pathway; E. determine if preconditioning can be induced in vitro, in another species. This new in vitro model will be useful in determination of mechanisms of endogenous cellular myocardial protection, which could allow development of a new class of therapeutic agents to reduce infarct size, or lead to better methods of organ preservation.

目标是确定预处理的机制 防止缺血性损伤。 预处理是指 对缺血性损伤的抵抗力，可以通过暂时性缺血引起， 在持续缺血之前，缺氧或腺苷A1受体。 在天然触发下，靶组织（神经，血管，肌细胞）都不是 或间质），也没有负责原位的机制 已经建立了预处理。 迄今为止，预处理只有 被证明发生在完整的心脏或动物中。 一个新的观察是 孤立的成年兔心肌细胞可以内源性预处理 通过短暂的，无基质的，氧化的局部局部缺血 潜伏期。 这种预处理授予高度的 随后的缺血（死亡延迟1-2小时）。 体外- 预处理机制与能源无关 利用/生产，或降低了降甲胺。 该提议着重于 这种新模型的表征，作为未来研究的基础 预处理的内源性细胞机制。 目的是 决定;答：保护与高能磷酸盐之间的关系 水平； B.如果扳机和保护与/不类似于 完整的心； C.如果在孵化后的预处理衰减 缺血之前； D.确定预处理的途径以及 蛋白质磷酸酶抑制剂会收敛到普通PKC相关途径； E. 确定在其他物种中是否可以在体外诱导预处理。 这种新的体外模型将有助于确定机制 内源性细胞心肌保护，这可以允许发展 一类新的治疗剂，可降低梗塞的大小或导致更好 器官保存的方法。