IONIC AND METABOLIC CHANGES IN ISCHEMIA AND REPERFUSION

在过去的30年里，已经开发出三种技术 为重新建立血液流动提供途径，以防止 潜在缺血心肌；1)冠状动脉搭桥术 移植(CABG)；2)血管成形术和其他介入治疗 技术；3)溶栓治疗。反映了临床上的成功，再次 建立灌流，有越来越多的研究 对了解缺血再灌流病理生理学的兴趣 心肌。此项目的总体目标是使用独立的 等容红细胞/白蛋白灌流(RBC-灌流)兔 大鼠心脏和离体缓冲液灌流技术的探索 这可能会提供有关离子的临床相关信息 以及由缺血和缺氧引起的代谢紊乱 再灌流。这个项目分为两个子项目 每个人都有两个明确的目标。第一个子项目将评估 2-氟-2-脱氧-D-葡萄糖(FDG)方法学 RBC灌流后外源性葡萄糖利用的定量研究 兔心。在具体目标1中，我们将首先评估FDG 三种示踪剂对冠状动脉血流量变化的探讨 动力学模型：1)索科洛夫-菲尔普斯；2)帕特拉克；3)冲量 回应。多指示剂稀释技术将是 用于研究因忽略而产生的潜在不准确性 目前PET和ANS的心内示踪剂弥散 FDG。我们还将把我们对FDG方法的分析扩展到 缺血后再灌流心肌。在具体目标2下，我们 将继续或评估使用FDG来定量葡萄糖 在低流量缺血和控制性缺氧中的应用。直接式 FDG示踪动力学模型的测试将在灌流后进行 PET扫描仪中的心脏将在项目II中建造。 将在核心A中对项目V中获得的数据进行分析 和项目III。中描述的灌流心脏方法学 项目四将利用项目五来分析 放射性标记的流动和线粒体示踪剂。

During the past 30 years, three techniques have been developed that provide avenues for re-establishing blood flow to jeopardized potentially ischemic myocardium; 1) coronary artery bypass grafting (CABG); 2) angioplasty and other interventional techniques; 3) thrombolysis. Reflecting the clinical success in re- establishing perfusion, there has been a growing investigative interest in understanding the pathophysiology of ischemic reperfused myocardium. The overall goal of this project is to use the isolated isovolumic red blood cell/albumin perfused (RBC-perfused) rabbit heart and isolated buffer perfused rat heart to explore techniques that might provide clinically relevant information about the ionic and metabolic derangements resulting from ischemia and reperfusion. This project has been divided into two subprojects with two specific aims each. The first subproject will evaluate the 2-fluoro-2- deoxy-D-glucose (FDG) methodology as a means of quantifying exogenous glucose utilization in the RBC-perfused rabbit heart. In Specific Aims 1 we will first evaluate the FDG approach at varying coronary blood flow rats using three tracer kinetic models: 1) Sokoloff-Phelps; 2) Patlak: and 3) impulse response. The multiple indicator dilution technique will be employed to study potential inaccuracies created by ignoring intracardiac tracer dispersion as currently practiced with PET an FDG. We will also extend our analysis of FDG methodology to the post-ischemic reperfused myocardium. Under Specific Aim 2, we will continue or evaluation of the use of FDG to quantitate glucose usage in low-flow ischemia and control-flow hypoxia. The direct testing of FDG tracerkinetic models will be done with perfused hearts in the PET scanner to be contructed in Project II. The analysis of data obtained in Project V will be performed in Core A and Project III. The perfused-heart methodology described in Project V will be utilized by Project IV for the analysis of radiolabeled flow and mitochondrial tracers.