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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032583-18
Application #
6638240
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Varghese, Jamie
Project Start
1984-07-01
Project End
2005-06-30
Budget Start
2003-04-01
Budget End
2005-06-30
Support Year
18
Fiscal Year
2003
Total Cost
$337,510
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Howard, Elliot J; Kerckhoffs, Roy C P; Vincent, Kevin P et al. (2013) Myofiber prestretch magnitude determines regional systolic function during ectopic activation in the tachycardia-induced failing canine heart. Am J Physiol Heart Circ Physiol 305:H192-202
Ashikaga, Hiroshi; Omens, Jeffrey H (2012) In vivo validation of longitudinal-circumferential area change ratio to estimate myofiber shortening in the heart. IEEE Trans Biomed Eng 59:1391-7
Chuang, Joyce S; Zemljic-Harpf, Alice; Ross, Robert S et al. (2010) Determination of three-dimensional ventricular strain distributions in gene-targeted mice using tagged MRI. Magn Reson Med 64:1281-8
Kerckhoffs, Roy C P; Omens, Jeffrey H; McCulloch, Andrew D et al. (2010) Ventricular dilation and electrical dyssynchrony synergistically increase regional mechanical nonuniformity but not mechanical dyssynchrony: a computational model. Circ Heart Fail 3:528-36
Raskin, Anna M; Hoshijima, Masahiko; Swanson, Eric et al. (2009) Hypertrophic gene expression induced by chronic stretch of excised mouse heart muscle. Mol Cell Biomech 6:145-59
Ashikaga, Hiroshi; van der Spoel, Tycho I G; Coppola, Benjamin A et al. (2009) Transmural myocardial mechanics during isovolumic contraction. JACC Cardiovasc Imaging 2:202-11
Campbell, Stuart G; Howard, Elliot; Aguado-Sierra, Jazmin et al. (2009) Effect of transmurally heterogeneous myocyte excitation-contraction coupling on canine left ventricular electromechanics. Exp Physiol 94:541-52
Coppola, B A; Omens, J H (2009) Use of Larger Species such as Dog and Pig as Model Systems to Study Cardiac Disease. Drug Discov Today Dis Models 5:195-200
Kerckhoffs, Roy C P; McCulloch, Andrew D; Omens, Jeffrey H et al. (2009) Effects of biventricular pacing and scar size in a computational model of the failing heart with left bundle branch block. Med Image Anal 13:362-9
Coppola, Benjamin A; Omens, Jeffrey H (2008) Role of tissue structure on ventricular wall mechanics. Mol Cell Biomech 5:183-96

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