ADENOSINE METABOLISM IN CARDIAC SURGERY

Understanding the relationship between energy metabolism and function in the postischemic heart continues to be our overall goal. Because we have found recovery from ischemia to require days, we have set up long-term clinically relevant models in order to study recovery. Our emphasis has not been on ways to prevent ischemic injury, but rather, on methods to enhance recovery and return of function. Our central hypothesis is that ischemia produces one or more defects in energy metabolism which contribute to the observed postischemic cardiac dysfunction. We will study postischemic energy metabolism and function in order to further define their relationship. Specifically we will: (1) Determine the postischemic myocardial energy production capacity in the intact animal by measuring ATP production and its regulation using 31P NMR spectroscopy. (2) Define the determinants of myocardial oxygen consumption (MVO2) in terms of functional and basal components. Function will be analyzed in terms of a stress-3 dimensional strain model. This will allow the mechanisms behind the inefficiency of postischemic function to be investigated. (3) Fine methods to enhance recovery of postischemic energy metabolism and cardiac function. These will include augmenting ATP recovery, increasing adenine nucleotide translocase activity and enhancing the levels of TCA cycle intermediates. (4) Determine the subcellular components of postischemic functional inefficiency, principally by studying calcium related events including the control of calcium fluxes and the function of the sarcoplasmic reticulum. In summary, determining the alterations in energy metabolism and function which characterize the postischemic myocardium and govern recovery should lead to a better understanding of their relationship. This will enable us to pursue our long range goal of designing clinically useable methods to improve recovery from ischemia.