Oxidation-reduction imaging of myoglobin unveils two-phase oxidation in the reperfused myocardium.

Abstract

Myocardial infarction (MI) is a serious cardiovascular problem that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dynamic and exhibits various oxidation-reduction states that have been a subject of attention in the food industry, specifically for meat consumers. However, rarely if ever, have the myoglobin optical properties been used to understand the pathology of MI. In the current study, we develop a novel imaging pipeline that integrates tissue clearing, confocal and light sheet fluorescence microscopy, combined with imaging analysis, and processing tools to investigate and characterize the oxidation-reduction states of myoglobin in the ischemic area of the myocardium post-MI. Using spectral imaging, we have characterized the endogenous fluorescence of the myocardium and demonstrated that it aligns with the spectral profile of myoglobin. Under ischemia-reperfusion experimental settings, we report that the infarcted myocardium spectral signature is similar to that of oxidized myoglobin signal that peaks 3 hours post-reperfusion and decreases with cardioprotection. These results were correlated with MI measurements by Late Gadolinium Enhancement MRI. In conclusion, this seminal work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estimating the size of the MI during early phases of reperfusion.