The overall objective of the proposed research is to understand the 3-dimensional dynamic geometry, and regional and global systolic mechanics of the human LV and RV in the context of cardiac disease and therapeutic interventions. Four interrelated projects will extend this work into promising, clinically relevant areas. This effort will take advantage of the unique capabilities of the myocardial marker technology to determine the 3-D instantaneous motion of multiple fixed intramyocardial sites in the hearts of intact human subjects and experimental animals. Project I investigates """"""""Valvular-Ventricular Interaction"""""""". Despite experimental evidence and clinical suggestions that preservation of the mitral chordae tendineae optimizes LV systolic function, MVR with excision of the subvalvular apparatus remains the standard procedure, and the mechanism whereby preservation of the chord is responsible for this salutary effect remains totally unknown. A series of animal and human protocols will address 6 hypotheses to elucidate the functional basis for this phenomenon (and the effects of rigid [prosthetic ring] annular fixation) in terms of 3-D dynamic LV geometry, local finite deformations, regional radii of curvature, and regional and global systolic LV mechanics. Project II examines the mechanisms of mitral regurgitation due to regional LV ischemia, the 3-D dynamics of direct intraventricular mechanical coupling (mechanical linkage) between ischemic and nonischemic areas, and the relationships between regional and global LV systolic performance. Three hypotheses will be tested in animal experiments and corroborated in patient studies. Project III addresses two hypotheses in animal and human experiments to determine: 1) The effects of (temporary or permanent) LVAD circulatory support on interventricular septal shifting and resultant RV/LV geometry changes, regional and global RV systolic mechanics, and septal contraction; and, 2) The effects of acute RV pressure overload on septal shifting, regional LV systolic mechanics, finite deformations, and dynamic 3-D geometry.Project IV is directed towards mapping, for the first time in the human LV, regional finite deformations and radii of curvature throughout the cardiac cycle. Regional principal correlated with regional transmural finite deformations to understand better the relation between LV anatomy and dynamics. The effects on regional strains and curvatures of alterations in preload, afterload, contractility, ventricular excitation sequence, and septal geometry (accompanying alterations in transseptal pressure gradients) will be examined. The studies have important implications for the understanding of the geometric design, shape, and functional dynamics of the human ventricular myocardium in both health and disease.
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| Stephens, Elizabeth H; Fahrenholtz, Monica M; Connell, Patrick S et al. (2015) Cellular and Extracellular Matrix Basis for Heterogeneity in Mitral Annular Contraction. Cardiovasc Eng Technol 6:151-9 |
| Stephens, Elizabeth H; Connell, Patrick S; Fahrenholtz, Monica M et al. (2015) Heterogeneity of Mitral Leaflet Matrix Composition and Turnover Correlates with Regional Leaflet Strain. Cardiovasc Eng Technol 6:141-50 |
| Kvitting, John-Peder Escobar; Kari, Fabian A; Fischbein, Michael P et al. (2013) David valve-sparing aortic root replacement: equivalent mid-term outcome for different valve types with or without connective tissue disorder. J Thorac Cardiovasc Surg 145:117-26, 127.e1-5; discussion 12 |
| Rausch, Manuel K; Famaey, Nele; Shultz, Tyler O'Brien et al. (2013) Mechanics of the mitral valve: a critical review, an in vivo parameter identification, and the effect of prestrain. Biomech Model Mechanobiol 12:1053-71 |
| Bothe, Wolfgang; Miller, D Craig; Doenst, Torsten (2013) Sizing for mitral annuloplasty: where does science stop and voodoo begin? Ann Thorac Surg 95:1475-83 |
| Rausch, Manuel K; Tibayan, Frederick A; Ingels Jr, Neil B et al. (2013) Mechanics of the mitral annulus in chronic ischemic cardiomyopathy. Ann Biomed Eng 41:2171-80 |
| Tsamis, Alkiviadis; Cheng, Allen; Nguyen, Tom C et al. (2012) Kinematics of cardiac growth: in vivo characterization of growth tensors and strains. J Mech Behav Biomed Mater 8:165-77 |
| Rausch, Manuel K; Tibayan, Frederick A; Miller, D Craig et al. (2012) Evidence of adaptive mitral leaflet growth. J Mech Behav Biomed Mater 15:208-17 |
| Swanson, Julia C; Krishnamurthy, Gaurav; Itoh, Akinobu et al. (2012) Vagal nerve stimulation reduces anterior mitral valve leaflet stiffness in the beating ovine heart. J Biomech 45:2007-13 |
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