Analysis of coronary microcirculation and myocardial crossbridge dynamic using SPring-8 synchrotron facility

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Global dynamics of coronary circulation and cardiac contraction have been well documented in cardiology and circulatory physiology. Recently, transmural, i.e., from epicardial to endocardial heterogeneities have been getting more important for better understanding of the cardiac pathophysiology. Thus the objective of this study was to reveal the detailed transmural characteristics of the myocardial crossbridge dynamics and the coronary micro-circulation.Firstly, we found that the diastolic predominant flow pattern was common throughout myocardial layers. During systolic phase, significant systolic reverse flow was observed in subendocardial arterioles, whereas a remarkable forward flow was observed in subepicardial arterioles. Intramural pressure gradient and myocardial stiffness (elastance) cause these transmural dissociations in systolic flow direction. We also found the vessel size dependent coronary vascular regulation system, and spatial and temporal myocardial flow heterogeneity using the SPring-8, custom-made intravital CCD microscopes, and molecular isotope tracers.Secondly, we revealed the transmural difference of crossbridge dynamics using the SPring-8. During contraction phase, subepicardial and midcardial crossbridge dynamics were harmonized well each other and synchronized with the left ventricular pressure development. However the crossbridge of deeper myocardium decayed earlier than that of subepicardium during relaxation phase. Earlier relaxation in the myocardium in deeper regions seemed to be beneficial for diastolic blood inflow into deeper myocardium.We are now going to promote the "Physiome" as the quantitative and integrated description of the functional behavior of the physiological state. We believe that the present studies contribute to the cardiovascular physiome in the sense that it clarified the close coupling between coronary microcirculation and actin-myosin macromolecular dynamics. (256/300 words)