PRECONDITIONING, ISF ADENOSINE, AND CARDIOPROTECTION

预适应、ISF 腺苷和心脏保护

基本信息

批准号：
2519322
负责人：
David G Van Wylen
金额：
$ 13.49万
依托单位：
ST. OLAF COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-01-01 至 1999-08-31
项目状态：
已结题

项目摘要

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、长期目标是阐明腺苷的心脏保护作用并增强我们对缺血预适应过程中发生的细胞事件。在拟议的研究，心脏微透析探针将被植入心内膜和心外膜提供变化的透壁轮廓间质液（ISF）中腺苷、腺苷代谢物的水平，局部心肌缺血期间和之后的乳酸和去甲肾上腺素在麻醉的动物中。微透析探针也将用于评估动脉和冠状静脉腺苷水平。心脏保护将通过局部心室功能的恢复和大小来评估 60 分钟局部心肌梗塞后的心肌梗塞缺血。实验方案将解决两个主要目标：目标 1. 确定冠状动脉内分级之间的关系腺苷给药和以下方面的变化：1) ISF 和冠状静脉腺苷，和； 2）心肌保护程度。目标 2. 确定缺血预处理诱导 ISF 腺苷短暂增加以及随后长时间的心肌保护程度缺血。拟议的实验将评估腺苷对于缺血的假设通过提供支持或反对该概念的直接证据来进行预处理这是缺血前 ISF 中腺苷的浓度它预先调节心脏并提供心肌保护。像这样，这些实验对于我们理解戏剧性的事件是如何发生的非常重要预处理提供的保护可以转化为临床情态。拟议的实验还将确定是否外源腺苷减少缺血引起的去甲肾上腺素释放，如果预处理通过减少去甲肾上腺素来部分保护心脏在随后的长时间缺血期间释放。