The ventricular myocardium consists of a syncytium of myocytes organized into branching, transmurally oriented laminar sheets approximately four cells thick. Recent evidence indicates that systolic shear and stretch of this laminar structure explains the nearly four fold difference between measured ventricular wall thickening and that which can be attributed to systolic myocyte thickening alone. lit is estimated that systolic rearrangement of the laminar architecture accounts for nearly half of the normal cardiac output. Although the initial insult may vary most forms of cardiac pathology (e.g. heart failure) we are associated with a progressive loss of ventricular function. In the present study we propose to test the overall hypothesis that changes in the architecture of the wall contribute importantly to this progressive loss of function. We propose to test the hypothesis that acute and chronic changes in the end diastolic orientation of the laminae alters the contribution of sheet shear to systolic wall thickening. We propose that decreases in ventricular volume and chronic remodeling of the diastolic orientation of the laminae towards a more radial direction will reduce the contribution of sheet shear to systolic wall thickening. Moreover, we propose that changes in the interlaminar stiffness induced by alterations in the extracellular matrix (ECM) may enhance (ischemia reperfusion injury - reduced ECM) or reduce (multiple infarctions and increases in the ECM) the contribution of laminar shear to wall thickening. These studies will be conduced in acute and chronic studies in dogs where sheet architecture and deformation can be measured and the contribution of shear and sheet position to wall thickening directly assessed. And in finite element models of the heart which accurately reflect both the geometry and deformation of the ventricular wall and allow one to test both the effects of changes in the architecture of the wall and alterations in stiffness that are not possible to achieve in vivo.
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