This project continues the theme of relating the behavior of the whole left ventricle to its constituent cardiac muscle fibers. Two distinct topics have been targeted. The first asks: How similar (or different) are the amounts of shortening and end-systolic segment lengths of muscle fibers in various layers (transmurally) or regions of the left ventricle? The more homogeneous the distribution, the more the behavior of the whole ventricle will correspond to that of its muscle fibers (after transforming for geometry). However, in a heterogeneous population, alterations in the distribution as chamber volume increases (by recruitment of short sub-endocardial fibers, for example) would provide another mechanism for the Frank-Starling law of the heart. To study the patterns of segment lengths and shortening in the beating heart, we will combine radiological and histological approaches. Small beads inserted into canine myocardium will be tracked via biplane cineradiography and an automated marker- locating system. The patterns of strain in several myocardial layers will be observed throughout the cardiac cycle in isolated canine hearts, while simultaneously monitoring and controlling ventricular pressure and volume. The second topic explores implications of the delayed-force property of myocardium. While well acknowledged as a fundamental property of striated myofilaments, the implications of delayed force for cardiac mechanics have never been fully considered. Recent ventricular studies by this laboratory suggest that it plays an important role in determining end-systolic pressure. Possibly, by retaining later into systole some of the force-generating potential developed at the initial stretched length, delayed force could provide a mechanism to oppose the deactivating effects of shortening. Hence, the physiologic basis for end-systolic pressure-volume relations may rest partially on a balance between these opposing effects -- a balance that might be disturbed by disease. Since this is such a fundamental question, it will be investigated initially in excised papillary muscles. To avoid end artifacts, a healthy central segment of the muscle will be defined by inserting two pins into the muscle and tracking their locations electro-optically. Predicted effects of delayed force (such as more end-systolic force with moderate shortening than in isometric contraction, history-dependent variations in force-velocity relations, etc.) will be tested. Moreover, we will examine whether these effects alter as predicted by the delayed force concept when the time-course of contraction is changed.
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