Early reperfusion is the best therapy for myocardial infarction (MI). Effectiveness, however, varies significantly between patients and has implications for long-term prognosis and treatment. A technique to assess the extent of myocardial salvage after reperfusion therapy would allow for high-risk patients to be identified in the early post-MI period. Mitochondrial dysfunction is associated with cell death following myocardial reperfusion and can be quantified by fluorometry. Therefore, we hypothesized that variations in the fluorescence of mitochondrial nicotinamide adenine dinucleotide (NADH) and flavoprotein (FP) can be used acutely to predict the degree of myocardial injury. Thirteen rabbits had coronary occlusion for 30 min followed by 3 h of reperfusion. To produce a spectrum of infarct sizes, six animals were infused cyclosporine A prior to ischemia. Using a specially designed fluorometric probe, NADH and FP fluorescence were measured in the ischemic area. Changes in NADH and FP fluorescence, as early as 15 min after reperfusion, correlated with postmortem assessment infarct size (r=0.695, p<0.01). This correlation strengthened with time (r=0.827, p<0.01 after 180 min). Clinical application of catheter-based myocardial fluorometry may provide a minimally invasive technique for assessing the early response to reperfusion therapy. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of the University of Pennsylvania's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to pubs-permissions@ieee.org. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.
A direct, noninvasive method of assessing the oxidation-reduction potential of an intramyocardial respiratory chain component is described. The technique is based on the differences in spectral properties between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NADH). The tissue surface fluorescence from intracellular NADH may be measured and documented photographically. Noose occlusion of a coronary artery produced detectable NADH fluorescence in 15 seconds in the subtended ischemic epicardium. This fluorescence of reduced pyridine nucleotide resolved following 60 seconds of reperfusion of the ischemic myocardium. The reduction of epicardial NADH with ischemia is a rapid and reversible process. A subsequent noose reocclusion resulted in a reproducible pattern of fluorescence. The technique of NADH fluorescence photography appears superior to current methods of assessing tissue oxygen supply:demand.
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