CONTROL OF BRAIN ENERGY METABOLISM

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This proposal describes a new method for stabilizing the energy state of the brain that is threatened by hypoxic distress due to failure of adequate O2 delivery. The energy state of the brain is evaluated by 31P NMR every 2 to 4 minutes and the ratio of phosphocreatine (PCr) to inorganic phosphate (Pi) or to adenosine triphosphate (ATP) is employed as a quantitative measure of this energy state. Model studies show that values for PCr/Pi above 1.0 afford stable function of brain (and heart) metabolism and values below 1.0 appear to be insufficient for long-term organ survival. Variation of the oxygen delivered to the tissues (FiO2) will control this ratio particularly in cases of insufficient lung function as in respiratory distressed neonates, but not limited thereto. The specific proposal for Phase I involves the testing of the manual control of FiO2 in response to the need for heart or brain PCr/Pi values that are above 1.0 first in animal models, secondarily (Phases iI and II) in respiratory distressed neonates and, as larer magnets become available, in adults who require oxygen therapy. Servo control of the brain or heart energy state is described and represents the seond phase (II) of development that affords an automatic control and presentation of even momentary loss or organ energy states in patients with diseases of O2 delivery to tissue.