Pathophysiological analysis of myocardial dysfunction by observing nanometer ordernanometer-order dynamics of actin-myosin, interaction

点击翻译按钮获取中文摘要

We have been proceeding to investigate into the cardiac physiology, especially in the myocardial excitation-contraction coupling. We study the cardiac performance in the isolated and in the in situ heart, theoretically analyze the data from the view of mechanoenergetics, and then speculate the myocardial intracellular Ca2+ dynamics and the myofilament crossbridge attach/detach kinetics. Then we found that the left ventricular myocardial intracellular Ca2+ dynamics is independent of the left ventricular volume and the left ventricular myofilament Ca2+ bound/unbound kinetics is also independent of the left ventricular volume. Then we proposed that the volume dependent increase in the cardiac contracting force that is known as Frank-Starling law is greatly dependent on the actin-myosin interaction. Several methods have been reported to investigate the actin-myosin interaction in variable level, most of them are the molecular level experiments. Tb investigate the myocardial actin-myosin in … More teraction in the physiologically contracting preparation, the x-ray diffraction technique is quite useful and reliable using synchrotron radiation. The x-ray provided by the first- and the second-generation synchrotron facilities were not enough strong to penetrate the myocardium and not enough monochromatic to make dear diffraction images. Because of these reasons, the investigators had to use thin papillary muscle and perform summation of diffraction images obtained from thousands of contractions to reduce S/N ratio. Now we can use the third generation synchrotron facility. Because the SPring-8 that is the world largest synchrotron facility can provide the ideal-ray characterized as 1) high photon flux, 2) monochromatic, and 3) collimated, we can analyze the actin-myosin interaction in the excised rat hearts in a single contraction without summation. We aimed to establish the x-ray diffraction analysis in isolated rat hearts and to analyze the relation between the left ventricular pressure and the actin-myosin interaction in the failing heart. The detailed results are in the main part of this report. Less