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

使用 SPring-8 同步加速器设备分析冠状动脉微循环和心肌桥动态

基本信息

批准号：
13854030
负责人：
KAJIYA Fumihiko
金额：
$ 58.24万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (S)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

项目摘要

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)

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记录。近年来，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变得越来越重要。因此，本研究的目的是揭示心肌过桥动力学和冠状动脉微循环的详细跨壁特征。首先，我们发现舒张期优势血流模式在整个心肌层中都很常见。在收缩期，心内膜下小动脉有明显的收缩反向血流，心外膜下小动脉有明显的正向血流。壁内压力梯度和心肌刚度（弹性）导致收缩血流方向上的跨壁解离。我们还使用SPring-8、定制的活体CCD显微镜和分子同位素示踪剂发现了血管大小依赖的冠状动脉血管调节系统，以及心肌血流的时空异质性。其次，我们利用SPring-8揭示了过桥动力学的跨壁差异。在收缩期心外膜下和心中交叉桥动力学协调良好，并与左室压力发展同步。而在松弛期，深层心肌的交桥比心膜下的交桥衰减得早。较早的深层心肌松弛似乎有利于舒张期血液流入深层心肌。我们现在将推广“生理组”作为生理状态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组，因为它阐明了冠状动脉微循环与肌动蛋白-肌球蛋白大分子动力学之间的密切耦合。(256/300字)