The proposed study will examine the metabolic response of the myocardium under the stress of ischemia. Metabolites will be measured by 31P NMR spectroscopy permitting measurement without the need for biopsy. This will enable repeated measurements over time in response to graded stimuli, and a careful observation of recovery. In vivo intact canine hearts will be examined via two NMR detection methods. The first will use the catheter-coil technique in which a coil is advanced through a peripheral blood vessel to the heart. Refinement of this technique represents one of the project aims, permitting spectra from localized myocardial regions to be collected without the need for major surgery and in times which are practical for the examination of the stressed myocardium. The second method involves the placement of epicardial surface coils at the time of thoracotomy. The combination of these two methods permits selective observation of signal from tissue at various depths from the subendocardium to the subepicardium. Spectra will be collected from myocardial regions subjected to graded ischemia using a balloon occluder placed on a proximal coronary segment, and the myocardium will be further stressed by rapid pacing. Adjacent areas will also be investigated and results correlated with tissue perfusion as measured by the microsphere technique. Additionally, function will be determined by radionuclide ventriculography to assess wall motion in the observed area. The overall objective of this proposal is to study cardiac ischemia and its transient and persistent effects on myocardial function. This information is intended to assist in the diagnosis and management of ischemia, and may enable others to develop new treatment regimens to either prevent or limit myocardial infarction.
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