AGE, REACTIVE OXYGEN METABOLITES AND MYOCARDIAL INJURY

本研究的总体目标是确定活性氧的作用 在未成熟和成熟的心脏心肌细胞损伤的代谢产物。 我们 已经表明，分离的未成熟兔心脏对一种 缺血再灌注的周期比成熟心脏长。 的基础 该容限是未知的。 周期性心肌细胞损伤 已知局部缺血和再灌注部分是由生成的 活性氧代谢物的含量 我们已经证明了电子自旋 共振（ESR）光谱可以检测自由基的产生， 离体灌流的大鼠和兔心脏。 本研究的目的是 测试心肌成熟需要改变的假设， 心肌对活性氧代谢产物的反应， 缺血再灌注的循环 我们将确定 对缺血/再灌注反应改变的转变， 功能标准。 然后我们将评估自由的物种和程度 自由基和顺磁性代谢物存在于心肌中， 过渡前有氧灌注/缺血/再灌注循环， 过渡期和过渡期后年龄，然后（具体目标3）评估 抗活性氧代谢物的防御机制 有氧灌注/缺血/再灌注循环。 最后，我们将评估自由基和 氧化剂通过灌注冠状动脉将对体内有氧功能产生影响 离体心脏的系统与这些代理。 这一假设将是 在一个物种兔子身上做了测试 孤立的工作心脏 准备将用于促进离散良好控制 观察有毒自由基物种的产生和防御 抗活性氧代谢物的机制，因为这些与 成熟过程 ESR光谱最近被我们用来 直接检测离体心脏中的自由基种类，并将用于 提供了自由基和顺磁性代谢产物的直接证据 在缺血和再灌注过程中的生成在未成熟中比在未成熟中少。 不成熟的心脏对自由基的耐受性更强 和氧化剂的产生比成熟的心脏， 标准，以及防御机制对压力造成的反应性 氧代谢物在成熟的心脏中比未成熟的心脏消耗得更多， 成熟的心，并将提供一个数据基础的发展战略 以改善缺血和再灌注期间的心肌保护。

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.