CITRIC ACID CYCLE METABOLISM DURING CARDIAC SURGERY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一系列量化底物利用的研究，旨在补充在常规心脏手术中遇到的条件下心肌缺血期间丢失的柠檬酸循环中间体。这些实验是使用隔离的灌流大鼠心脏制剂进行的，涉及到标记底物和核磁共振光谱的使用。我们研究了多种柠檬酸底物在稳定状态下的氧化和复苏，以及在各种心脏停搏液的设置中和缺血后的情况。具体地说，将研究心脏停搏液的代谢效应，首先在对照心脏，然后在服用1)温持续性钾停搏液，2)细胞内停搏液，3)低钠低钾停搏液，4)钾停搏液加河豚毒素以实现极化停搏，5)钾通道开放剂吡那地尔实现超极化停搏，以及6)清洗和包装猪红细胞以评估红细胞对细胞代谢的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a series of studies which quantify substrate utilization in pathways designed to replete citric acid cycle intermediates lost during myocardial ischemia under conditions encountered during routine cardiac surgery. The experiments are 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 are 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 metaboli