This project focuses on the structure-function relationship of the left ventricle. Its ultimate aim is to understand how the cellular process of individual sarcomere contraction integrates to produce the mechanical pump function of the whole left ventricle. Within the myocardium, sarcomere contraction deforms the intra- and extracellular passive matrix. Also, sarcomeres from one layer interact with others in adjacent layers (transmurally) and in neighboring and remote regions of the heart. Not only is understanding these local and remote interactions in the normal heart critical for relating normal cardiac function to sarcomere function; the observations will also establish the normal baseline against which the distortions produced by regional ischemia can be compared. By combining cineradiography of implanted markers with postmortem histology of the implanted region, local sarcomere lengths and orientation; can be reconstructed. Thus, this technique offers the first opportunity to visualize the dynamic shortening and lengthening of myocardial sarcomeres while they actively contract within the ventricular wall. Simultaneously, the three-dimensional deformation of myocardial tissue parallel and perpendicular to sarcomeres will be determined. Measurements of both sarcomere and local tissue deformation will be correlated with the global changes in chamber volume measured in isolated, supported canine hearts that are exposed to a wide range of simulated hemodynamic loads. Specifically, the following questions will be examined: 1) As sarcomeres contract more or less vigorously, is the pattern of sarcomere and tissue deformation altered for the same chamber volume? 2) Comparing regions, do local deformations relate similarly to volume, or, alternatively, are there changes (a) between apex and base, and (b) between septum and free-wall? Next, using """"""""tagged"""""""" magnetic resonance images having a specially developed, high-resolution grid, deformation measurements will then be extended throughout equatorial and subapical cross-sections to verify that the trends observed in isolated hearts carry over in situ. Predicting local deformations and stresses (e.g. , the """"""""restoring"""""""" stresses generated in passive tissue components by sarcomere contraction) demands knowledge of the stress-strain laws governing myocardial mechanical behavior. By observing the relation between torsional vs. extensional stiffness of papillary muscles, (1) the stress-strain laws of active myocardium under controlled multi-axial loads, and (2) the shearing stresses developed in passive myocardium will be determined.
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