Diagnostic and quantitative of cardiac viability following acute ischermia help in determining therapeutic strategies and ultimately, influence the clinical outcome. The long-term objective of this project is noninvasive ultrasonographic detection and quantitation of characteristic local mechanical patterns that reflect myocardial metabolic activity, the principal determinant viability. We found that experimental pharmacologic inhibition of myocyte energy metabolism in s selected myocardial region leads to reproducible intramyocardial mechanical aberrations. In particular, there is a graded delay in the onset of energy-dependent myocardinal relaxation. Amplitude and discrete timing of these local functional events in measurable using novel Doppler myocardial velocity gradient (MVG) echocardiography. Based on these findings, we propose a new concept of linking specific mechanical patterns of local myocardinal relaxation to myocyte energy metabolism. Such mechanical patterns could serve as diagnostic markers of continuing myocardial viability during acute ischemia. We hypothesize that the characteristic local mechanical aberrations, measured noninvasively in vivo will correlate with measures of myocyte energetics, assayed in vitro. The short-term goal is to study the relationship between 1) functional parameters of MVG echocardiography, such as a) time to the point of transition from contraction to relaxation, b) postsytolic contraction amplitude, and c) magnitude of early relaxation; and 2) simulataneous measures of myocyte energy metabolism. The accepted measures are a) adenosine triphosphate turnover, b) creatine phosphate/ inorganic phosphate ratio, and c) creatine kinase activity. Aim1: Quantitate local myocardial mechanical patterns associated with induced anaerobic metabolic stress. Aim2: Quantitate intramyocardial mechanical patterns of altered myocyte metabolism in acutely progressively ischemic myocardium. Aim3: Quantitatively characterize mechanical patterns of altered energy metabolism in stunned, hibernating, and reperfused myocardium. These aims will be accomplished A) using open- chest pig models of acute myocardial energy metabolism stress, B) measuring the myocardial mechanical aberrations with high temporal and spatial resolution MVG echocardiography, and C) correlating the MVG data to high-energy phosphate levels in cardiac biopsies analyzed by spectrophotometry. This proposal is designed to study a novel principle of myocardial aberrations reflecting preserved myocyte energetic turnover during acute anaerobic and aerobic metabolic stress. This research is fundamentally important for understanding cardiac viability and essential for defining the underlying pathophysiologic mechanism of a discrete myocardial functional response to acute ischemia.
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