Phosphorus nuclear magnetic resonance (31P NMR) is to be used in measuring dynamic metabolic events in perfused rabbits hearts. Drugs commonly applied in treatment of cardiac disease will be examined in this manner to assess their effects in well perfused hearts. 31P surface coil NMR will then be used to investigate in vivo high energy phosphorylated substrate metabolism in small, spatially selected regions of perfused rabbit hearts. This study is intended to provide new information about issues central to understanding and treating acute myocardial infarction. The focus in on the issues: To what extent is there an "ischemic border zone" of reversibly impaired myocardium surrounding the central ischemic region? What can be done to save this tissue and reduce the overall damage to myocardium from acute infarction? And, what are the time-dependent metabolic consequences of common drug therapies used inthe clinical management of acute infarction on the central ischemic and border zone? Previous studies of regional ischemia and the ischemic "border zone" have relied upon analysis of biopsy tissue specimens obtained at specified times or upon limited in vivo data (NADH fluorescence, implanted peizo-electric transducers). NMR methods permit the serial and essentially continuous localized measurement of phosphate metabolism prior to an for extended periods following myocardial infarction. For the studies proposed herein, high resolution 31P NMR spectra from selected regions of perfused rabbit hearts will be obtained using surface coils. Two surface coils will be multiplexed to obtain "simultaneous" spectra from two different regions of the heart. Creatine kinase kinetics, and possibly rates of ATP Gamma-P exchange, will be determined in situ by the method of saturation transfer. Biochemical analyses of tissue samples will be done order to provide insight and explanation for observed alterations in relaxation and creatine kinase kinetic parameters in ischemically injured and drug-treated myocardium. Other factors such as edema, tissue levels of divalent cations and total protein content will be correlated with NMR measurements.
NIH ExPorter
NIH ExPorter