CITRIC ACID CYCLE METABOLISM DURING CARDIAC SURGERY

心脏手术期间的柠檬酸循环代谢

• 批准号: 2857902
• 负责人: MICHAEL E JESSEN
• 金额: $ 12.35万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-15 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2857902
• 关键词: Krebs' cycle; acyl coA; aminoacid; aspartate; carbohydrate transport; fatty acid metabolism; glutamates; guanidines; heart arrest; heart cell; heart function; heart metabolism; heart surgery; laboratory rat; lipid transport; myocardial ischemia /hypoxia; myocardium; nuclear magnetic resonance spectroscopy; oxidation reduction reaction; oxygen consumption; potassium channel; propionates; pyruvates; reperfusion; sodium

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.

描述：（改编自研究者摘要）本研究者 提出了一系列的研究，将量化基板利用率， 旨在补充柠檬酸循环过程中损失的中间体的途径 在常规心脏检查中遇到的条件下的心肌缺血 手术 拟议的实验将使用一个孤立的 灌注的大鼠心脏制备物，并涉及使用标记的底物， 核磁共振波谱法。 多种柠檬酸底物的氧化， 回补作用将在稳态下以及期间和之后进行研究 在各种心脏停搏液的设置中的局部缺血。 具体地说， 将研究心脏停搏液的代谢效应，首先在对照组中， 心脏，然后在心脏中给予1）温暖的持续钾 心脏停搏液，2）细胞内心脏停搏液，3）低钠 低钾停搏液; 4）河豚毒素钾停搏液 5）钾通道开放剂吡那地尔 以实现超极化阻滞，以及6）清洗并包装猪 红细胞，以评价红细胞对细胞的影响， 新陈代谢. 一旦这些干预措施的代谢效应被消除， 确定，钾心脏停搏液实现的机制 抑制脂肪酸氧化和刺激回补作用， 使用不能通过回补进入TCA循环的底物进行研究 途径。 还将在灌注心脏中进行研究， 标记丙酮酸以检测外源性 丙酮酸 实验的下一阶段包括评估 心肌缺血后灌注钾停搏液对心肌代谢的影响。 最后，心脏停搏组合物将被改变为包括谷氨酸和谷氨酸。 天冬氨酸。 这些研究将旨在确定 代谢和功能，并进一步消除作用机制。 是 预计这些发现将提供有关代谢的新信息。 对保持或增强细胞能量很重要的机制 店 这反过来又会导致心脏停搏液的改善 目前使用的解决方案。