The goal of this project is to develop an implantable combination lactate/oxygen sensor that can continuously and simultaneously monitor blood lactate and oxygen concentration. This project will use and integrated approach of engineering and physiological techniques aimed t development of an acceptable biosensor that can be used for basic research applications and for clinical m monitoring in critical care units. There is a need in research and clinical medicine for an implantable lactate/oxygen sensor which can continuously monitor lactate and oxygen concentration at specific sits in the body. Hypoxic and ischemic conditions cause significant changes in blood lactate concentration. The role of lactate concentration as indicator in these labile conditions can be investigated dynamically with the combination in vivo lactate/oxygen sensor as proposed here. This sensor has potential diagnostic, prognostic and therapeutic value for myocardial ischemia, circulatory shock, acidosis, exercise physiology, cardiac rehabilitation, surgery and neonatal monitoring. A systematic approach of theoretical modeling, in vivo experiments will be used to develop a reliable lactate sensor. A mathematical model that describes the physical and chemical process within the sensor will be use for sensor design and signal interpretation. This model will predict the influence of pertinent sensor parameters (geometric, diffusive, kinetic, and equilibrium) on the sensor response. This direct modeling approach for sensor design and signal interpretation avoids the time consuming trial and error approach commonly used in biosensor development. In vitro experiments will be conducted with sensors that are fabricated having the design features suggested from the modeling studies, the purpose of the in vitro experiments is to completely characterize the sensor response and validate the sensor design before the sensor is implanted, After the sensor design is refined by the modeling and in vitro experiments, the sensor will be assessed for their performance in blood during intravascular implantation in dogs and rats. These implant studies will allow evaluation of the enzyme catalytic lifetime chemical interference, biocompatibility and overall sensor reliability. The fully characterized sensor will then be used in studies of myocardial ischemia and in the evaluation of blood substitutes.