PRECONDITIONING, ISF ADENOSINE, AND CARDIOPROTECTION

预适应、ISF 腺苷和心脏保护

• 批准号: 2222643
• 负责人: David G Van Wylen
• 金额: $ 12万
• 依托单位: ST. OLAF COLLEGE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2222643
• 关键词: adenosine; chemoprevention; conditioning; dipyridamole; dogs; heart circulation; heart function; heart metabolism; heart pharmacology; high performance liquid chromatography; histology; interstitial; isolation perfusion; lactates; microdialysis; myocardial infarct sizing; myocardial ischemia /hypoxia; myoglobin; norepinephrine

The broad, long-term aims of the proposed research are to elucidate the cardioprotective actions of adenosine and to enhance our understanding of the cellular events which occur during ischemic preconditioning. In the proposed research, cardiac microdialysis probes will be implanted in the endocardium and epicardium to provide transmural profiles of the changes in interstitial fluid (ISF) levels of adenosine, adenosine metabolites, lactate, and norepinephrine during and after regional myocardial ischemia in anesthetized animals. Microdialysis probes will also be used to assess arterial and coronary venous adenosine levels. Cardioprotection will be evaluated by the recovery of regional ventricular function and by the size of the myocardial infarction following 60 minutes of regional myocardial ischemia. The experimental protocols will address two primary aims: Aim 1. To determine the relationship between graded intracoronary adenosine administration and the changes in: 1) ISF and coronary venous adenosine, and; 2) the degree of myocardiaI protection. Aim 2. To determine the relationship between the magnitude of the transient increase in ISF adenosine induced by ischemic preconditioning and the degree of myocardial protection from subsequent prolonged ischemia. The proposed experiments will assess the adenosine hypothesis for ischemic preconditioning by providing direct evidence for or against the concept that it is the concentration of adenosine in the ISF prior to ischemia that preconditions the heart and affords myocardial protection. As such, these experiments are important to our understanding of how the dramatic protection afforded by preconditioning can be translated into a clinical modality. The proposed experiments will also determine if exogenous adenosine reduces the ischemia-induced norepinephrine release and if preconditioning protects the heart in part by reducing norepinephrine release during a subsequent period of prolonged ischemia.

拟议研究的广泛，长期的目标是阐明 腺苷的心脏保护作用，并增强我们对 缺血性预处理期间发生的细胞事件。 在 拟议的研究，心脏微透析探针将植入 心内膜和心外膜提供变化的透壁概况 在腺苷的间质液（ISF）水平中，腺苷代谢产物， 区域心肌缺血期间和之后的乳酸和去甲肾上腺素 在麻醉动物中。微透析探针也将用于评估 动脉和冠状静脉腺苷水平。 心脏保护将是 通过恢复区域心室功能和大小进行评估 在区域心肌60分钟后，心肌梗塞的梗塞 缺血。实验协议将解决两个主要目的： 目的1。确定分级冠状动脉内的关系 腺苷给药和：1）ISF和冠状静脉的变化 腺苷，以及； 2）心肌保护程度。 目标2。确定幅度之间的关系 通过缺血性预处理引起的ISF腺苷的瞬态增加 以及随后延长的心肌保护程度 缺血。 提出的实验将评估缺血性的腺苷假说 通过提供或反对概念的直接证据来进行预处理 在缺血之前，是ISF中腺苷的浓度 这是前提的心脏，并提供心肌保护。 像这样， 这些实验对我们对戏剧性的理解很重要 预处理提供的保护可以转化为临床 方式。提出的实验还将确定是否外源 腺苷减少缺血诱导的去甲肾上腺素的释放，以及 预处理可以通过减少去甲肾上腺素来保护心脏 在随后的长期缺血期间释放。