During the past 30 years, three techniques have been developed that provide avenues for re-establishing blood flow to jeopardized potentially ischemic myocardium; 1) coronary artery bypass grafting (CABG); 2) angioplasty and other interventional techniques; 3) thrombolysis. Reflecting the clinical success in re- establishing perfusion, there has been a growing investigative interest in understanding the pathophysiology of ischemic reperfused myocardium. The overall goal of this project is to use the isolated isovolumic red blood cell/albumin perfused (RBC-perfused) rabbit heart and isolated buffer perfused rat heart to explore techniques that might provide clinically relevant information about the ionic and metabolic derangements resulting from ischemia and reperfusion. This project has been divided into two subprojects with two specific aims each. The first subproject will evaluate the 2-fluoro-2- deoxy-D-glucose (FDG) methodology as a means of quantifying exogenous glucose utilization in the RBC-perfused rabbit heart.
In Specific Aims 1 we will first evaluate the FDG approach at varying coronary blood flow rats using three tracer kinetic models: 1) Sokoloff-Phelps; 2) Patlak: and 3) impulse response. The multiple indicator dilution technique will be employed to study potential inaccuracies created by ignoring intracardiac tracer dispersion as currently practiced with PET an FDG. We will also extend our analysis of FDG methodology to the post-ischemic reperfused myocardium.
Under Specific Aim 2, we will continue or evaluation of the use of FDG to quantitate glucose usage in low-flow ischemia and control-flow hypoxia. The direct testing of FDG tracerkinetic models will be done with perfused hearts in the PET scanner to be contructed in Project II. The analysis of data obtained in Project V will be performed in Core A and Project III. The perfused-heart methodology described in Project V will be utilized by Project IV for the analysis of radiolabeled flow and mitochondrial tracers.
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