AGE, REACTIVE OXYGEN METABOLITES AND MYOCARDIAL INJURY

这项研究的总体目标是确定活性氧的作用。 未成熟和成熟心脏心肌细胞损伤中的代谢物。我们 已经表明，孤立的未成熟的兔心对 比成熟心脏的缺血和再灌流周期短。的基础 这种容忍度是未知的。一次循环的心肌细胞损伤 已知的缺血和再灌流的部分原因是 活性氧代谢物。我们已经证明了电子自旋 共振(ESR)光谱可检测人体内自由基的产生 分离灌流的大鼠和兔心。这项研究的目的是 检验心肌成熟需要改变的假说 心肌对活性氧代谢产物的反应 缺血和再灌流的循环。我们将确定……的年龄 对缺血/再灌流反应改变的转归 功能标准。然后我们将评估自由的种类和程度 心肌中存在的自由基和顺磁性代谢物 过渡前的有氧灌流/缺血/再灌流周期， 过渡年龄和过渡后年龄，然后(具体目标3)评估 机体对活性氧代谢物的防御机制 三个年龄组的有氧灌流/缺血/再灌流周期。 最后，我们将评估自由基和一种 氧化剂通过灌流冠状动脉对体内有氧功能的影响 与这些药物隔离的心脏系统。这一假设将是 在一种动物身上进行了测试，那就是兔子。孤立的工作心脏 准备工作将用来促进离散的良好控制 有毒自由基物种的产生和防御的观察 对抗活性氧代谢产物的机制，因为这些与 成熟的过程。电子自旋共振波谱最近被我们用来 直接检测离体心中的自由基物种，并将用于 为自由基和顺磁性代谢物提供直接证据 在缺血和再灌流期间，未成熟组的生成少于 成熟的心脏，即未成熟的心脏对自由基的容忍度更高 和氧化剂的生成比成熟心脏的功能评估要好 标准，以及对反应性压力的防御机制 成熟的心脏比未成熟的心脏消耗更多的氧代谢产物 成熟的心脏，将为制定战略提供数据基础 改善缺血再灌注期的心肌保护。

The overall goal of this study is to define the role of reactive oxygen metabolites in myocardial cell injury in immature and mature hearts. We have shown that the isolated immature rabbit heart is more tolerant to a cycle of ischemia and reperfusion than the mature heart. The basis for this tolerance is unknown. Myocardial cell injury induced by a cycle of ischemia and reperfusion is known to be caused in part by the generation of reactive oxygen metabolites. We have shown that Electron Spin Resonance (ESR) spectroscopy can detect free radical generation in isolated perfused rat and rabbit hearts. The aim of this study is to test the hypothesis that myocardial maturation entails an alteration in the myocardial response to reactive oxygen metabolites manifested during a cycle of ischemia and reperfusion. We will determine the age of transition for altered response to ischemia/reperfusion as assessed by functional criteria. We will then assess the species and extent of free radicals and paramagnetic metabolites present in myocardium during the cycle of aerobic perfusion/ischemia/reperfusion in pre-transition, transition and post-transition ages, and then (Specific Aim 3) assess the defense mechanisms against reactive oxygen metabolites during the aerobic perfusion/ischemia/reperfusion cycle in the three age groups. Finally we will assess the direct impact that free radicals and an oxidant will have on aerobic function in vivo by perfusing the coronary system of the isolated heart with these agents. This hypothesis will be tested in one species, the rabbit. The isolated working heart preparation will be used to facilitate discrete well-controlled observations of generation of toxic radical species and of defense mechanisms against reactive oxygen metabolites as these relate to the maturational process. ESR spectroscopy has recently been used by us to detect directly radical species in isolated hearts and will be used to provide direct evidence for free radical and paramagnetic metabolite generation during ischemia and reperfusion is less in immature than mature hearts, that the immature heart is more tolerant to free radicals and oxidant generation than the mature heart as assessed by functional criteria, and that defense mechanisms against stress caused by reactive oxygen metabolites are depleted more in mature hearts than immature and mature hearts and will provide a data base for development of strategies to improve myocardial preservation during ischemia and reperfusion.