Substrate Utilization During Hypothermia and Exposure to Thyroid Hormone, T3
Hypothermia is commonly used during cardiac surgery in order to protect the myocardium during ischemia. Hypothermia induces alterations in myocardial substrate metabolism, such as reduction in high-energy phosphate utilization and synthesis, and accumulation of harmful metabolites.
Thyroid hormone, triiodothyronine (T3), which functions as a physiological modifier in the hypothermic response, circulates at low levels after hypothermic cardiopulmonary bypass and ischemia. Therefore, inadequate thyroid hormone stimulation might deleteriously after efficiency of myocardial energy metabolism.
Recent findings in our laboratory regarding modification of myocardial metabolism by thyroid hormone compelled us to develop the hypothesis stating that: thyroid hormone modifies myocardial fatty acid utilization during and after hypothermia and ischemia. Consequently, the specific aims of this study are the following:
Substrate and temperature preferences and thyroid modulation of substrate utilization during hypothermia will be studied in the rat heart using 13-C magnetic resonance spectroscopy and isotopomer analysis. Studies will be conducted on isovolemic perfused rat hearts infused with physiological quantities of various substrates including glucose, lactate, acetoacetate, and free fatty acids.
