METABOLIC PHYSIOLOGY AND SIGNALS OF HEART/LUNG DISEASES

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Investigations proposed here continue a program to develop and apply new technologies for evaluation of the adequacy of tissue metabolic physiology and for early warning of diseases of heart and/or lungs as they impact on other tissues such as brain. Comparisons will be made of brain mitochondrial redox functioning under "resting" and "active" conditions to increase understanding of the physiological basis of metabolic monitoring, and thereby, to increase the sensitivity of these and other techniques, such as magnetic resonance spectroscopy (MRS), as indicators of metabolic dysfunction. These studies will lead to efforts to define the changes produced by systemic derangments that threaten metabolic integrity. The overall hypothesis of this research is that the onset and severity of brain metabolic insults that result from cardiopulmonary dysfunctions can be signalled by optical techniques that measure mitochondrial redox activity. Goals will be to develop optical techniques as "warning" indicators for early intervention when metabolic insufficiency is threatened with the ultimate objective of using techniques as end points for assessment of the extent of injury and for prognosis. Results of optical technologies, based upon rapid-scanning and reflectance spectrophotometry of cytochromes and fluorometry of pyridine nucleotides will be considered in the visible and infrared regions of the spectrum to account for light absorption and tissue scattering properties and to enhance the capability for non-invasive patient monitoring. Collaborative studies with investigators at other universities will provide a means to compare and correlate optical data with information derived from measurements of brain electrophysiology and of tissue metabolites by MRS. By monitoring metabolic functioning during cardiopulmonary insults which have the potential to cause serious damage to the brain and other vulnerable tissues, it will be possible to define the relative sensitivities of systemic vs tissue metabolic monitoring technologies and to determine the efficacy of each in signalling potential tissue injury when heart and/or lung dysfunctions threaten tissue oxygenation or respiration.