Quantifying Acute Myocardial Injury Using Ratiometric Fluorometry

Abstract

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.

The impact of aging, hearing loss, and body weight on mouse hippocampal redox state, measured in brain slices using fluorescence imaging

“…Cellular NADH can be quantified by measuring the emitted fluorescence in tissue at approximately 450 nm after excitation with wavelengths of approximately 350 nm (Duchen, et al, 2003, White and Wittenberg, 1993). Many investigators have used this ratio to measure oxidative stress across multiple tissue types, including brain (Gerich, et al, 2009, Gerich, et al, 2006, Maleki, et al, 2012, Mayevsky, 1984, Parihar, et al, 2008, Ranji, et al, 2009) and this ratio has been established to be directly associated with tissue oxidative stress (Crowley, et al, 2015, Salehpour, et al, 2015). We and others found that this ratio can be measured in acutely-prepared brain slices, and is sensitive to small perturbations of molecules known to cause oxidative stress, such as hydrogen peroxide and cyanide (Gerich, et al, 2009, Gerich, et al, 2006, Stebbings, et al, 2016).…”

On the Detection of Myocadial Scar Based on ECG/VCG Analysis

“…Obtaining this information allows identification of the cases where the implantation of an Implantable Cardioverter-Defibrillator (ICD) device would be beneficial. Imaging techniques such as Contrast-Enhanced Cardiac Magnetic Resonance Imaging (CMR) can provide detailed information on the presence, location and extent of myocardial scar [4], [5]. However, in addition to its suitability only as a bedside test, CMR is a resource-demanding process, both in terms of cost and specialized personnel required for its operation.…”

High-sensitive fluorescence endoscope using electrocardiograph-synchronized multiple exposure

“…In cardiac surgery, indocyanine green (ICG), which is a type of fluorescent substance, is used to confirm blood perfusion after CABG surgery [11,12]. Furthermore, some studies have reported that autofluorescence exists in the myocardium and can be used to reflect mitochondrial viability in real time [13,14]. Fukuhiro et al [13] examined the fluorescence of nicotinamide adenine dinucleotide (NADH) with a CCD camera and an ultraviolet excitation light in a rat heart.…”

“…They concluded that it was possible to evaluate the change of myocardial NADH fluorescence during myocardial ischemia. Ranji et al [14] developed a catheter-like fluorescence measuring probe using a photomultiplier tube for NADH and flavoprotein (FP) in the myocardium. This in vivo study in rabbit hearts showed that the ratio of NADH to FP reflected the size of ischemia.…”