CITRIC ACID CYCLE METABOLISM DURING CARDIAC SURGERY

描述：(改编自调查员摘要)这位调查员 提出了一系列研究，将量化底物利用率在 为补充柠檬酸循环中间产物而设计的途径 常规心脏手术中遇到的情况下的心肌缺血 做手术。拟议的实验将使用独立的 灌流大鼠心脏制剂，并涉及使用标记底物和 核磁共振波谱。多个柠檬酸底物的氧化和 复原力将在稳定状态下以及在过程中和之后进行研究 在各种心脏停搏液的设置下的缺血。具体来说， 心脏停搏液的代谢影响将首先在对照中进行研究。 心脏，然后在心脏中注入温热的持续钾 停搏液，2)细胞内停搏液，3)低钠 和低钾停搏液，4)含河豚毒素的钾停搏液 添加以实现极化停滞，5)钾通道开放剂吡那地尔 为了实现超极化停滞，6)清洗和打包猪 评价红细胞对细胞功能的影响 新陈代谢。一旦这些干预措施的新陈代谢效应 确定的，钾停搏液实现的机制 抑制脂肪酸氧化和刺激退行性变将是 使用不能通过逆蚀进入TCA循环的底物进行了研究 小路。研究也将在灌流的心脏中进行， 标记丙酮酸是为了检测外源激素的贡献 丙酮酸。实验的下一阶段包括评估 缺血后输注钾停搏液的代谢效应。 最后，心脏停搏药的成分将被改变，以包括谷氨酸和 天冬氨酸。这些研究将被设计用来确定 并进一步消除代谢和功能的作用机制。它是 预计这些发现将提供有关新陈代谢的新信息 对保存或增强细胞能量很重要的机制 商店。这反过来应该会导致心脏停搏的改善。 当前使用的解决方案。

DESCRIPTION: (Adapted from investigator's abstract) This investigator proposes a series of studies which will quantify substrate utilization in pathways designed to replete citric acid cycle intermediates lost during myocardial ischemia under conditions encountered during routine cardiac surgery. The proposed experiments will be conducted using an isolated perfused rat heart preparation and involve the use of labeled substrates and NMR spectroscopy. Oxidation of multiple citric acid substrates and anaplerosis will be studied under steady-state as well as during and after ischemia in the setting of various cardioplegic solutions. Specifically, the metabolic effects of cardioplegia will be studied, first in control hearts and then in hearts administered 1) warm continuous potassium cardioplegia, 2) an intracellular based cardioplegic solution, 3) low sodium and low potassium cardioplegia, 4) potassium cardioplegia with tetrodotoxin added to achieve polarized arrest, 5) the potassium channel opener pinacidil to achieve hyperpolarized arrest, and 6) washed and packed porcine erythrocytes to evaluate the effects of red blood cells on cellular metabolism. Once the metabolic effects of these interventions have been determined, the mechanisms by which potassium cardioplegia achieves suppression of fatty acid oxidation and stimulation of anaplerosis will be studied using substrates which cannot enter the TCA cycle via anaplerotic pathways. Studies will also be conducted in perfused hearts in which only pyruvate is labeled in order to detect the contribution of exogenous pyruvate. The next phase of the experiment includes evaluation of the metabolic effects of infusing potassium cardioplegia after ischemia. Finally, cardioplegic composition will be altered to include glutamate and aspartate. These studies will be designed to determine the linkage between metabolism and function and further eliminate mechanism of actions. It is anticipated that the findings will provide new information on the metabolic mechanisms that are important to preserving or enhancing cellular energy stores. This, in turn, should lead to improvements in cardioplegic solutions currently used.