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
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