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

冠状动脉循环和心脏收缩的整体动力学已经在心脏病学和循环生理学中得到了很好的证明。最近，跨壁，即，从心外膜到心内膜的异质性对于更好地理解心脏病理生理学变得越来越重要。因此，本研究的目的是揭示心肌桥动力学和冠状动脉微循环的详细的跨壁特征。首先，我们发现舒张期优势血流模式在整个心肌层中是常见的。在收缩期，心内膜下小动脉有明显的收缩期反向血流，而心外膜下小动脉有明显的收缩期正向血流。壁内压力梯度和心肌硬度（弹性）导致收缩期血流方向的跨壁分离。我们还发现了血管尺寸依赖性冠状动脉血管调节系统，空间和时间的心肌血流异质性使用SPring-8，定制的活体CCD显微镜，和分子同位素示踪剂。其次，我们揭示了跨桥动力学的跨壁差异使用SPring-8。在收缩期，心外膜下和中间横桥动力学相互协调，与左心室压力同步发展。而舒张期深心肌的跨桥比心外膜下的跨桥衰减早。较深区域心肌的早期舒张似乎有利于舒张期血液流入更深的心肌。我们现在要推广“生理组”作为生理状态的功能行为的定量和综合描述。我们认为，目前的研究有助于心血管生理学的意义上，它澄清了冠状动脉微循环和肌动蛋白-肌球蛋白大分子动力学之间的密切耦合。(256/300字）

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)