The global left ventricular dysfunction that is characteristic of left ventricular aneurysm (LVA) is associated with stretching of muscle fibers in the adjacent noninfarcted (border zone) region during isovolumic systole. The mechanism of this regional dysfunction is poorly understood, but it likely involves reduced myocardial contractility and increased myocardial stress in the border zone region during isovolumic systole. This proposed research investigates the role that myocardial material properties and stress play in the regional mechanical dysfunction of an experimental animal model of LVA. The long-term goal of this research is to use experimental and theoretical models to develop new operations for aneurysm repair. The experimental model for the proposed research is the anterioapical sheep aneurysm model (10 weeks after transmural infarction). First, using magnetic resonance imaging tissue tagging, myocardial deformation will be measured in orthogonal sets of images throughout the ventricular walls of in vivo hearts; with and without LVA. Next, the material properties of infarcted, border zone, and remote noninfarcted regions in isolated arrested hearts with LVA, as well as those of corresponding regions in isolated arrested normal hearts, will be determined using our novel approach to mechanical testing (""""""""epicardial suction""""""""), which leaves the ventricular walls intact and introduces a complex (bending and shearing) mode of deformation in the region of interest. Then, these passive material properties will be used in an existing state-of-the-art finite element model for the mechanics of the beating ventricles to compute three-dimensional myocardial stress and deformation throughout the ventricular walls of in vivo hearts; with and without LVA. The measurements of in vivo myocardial deformation will be used to validate the systolic material properties of the model. Finally, the first realistic models of the conventional aneurysm repair and the state-of-the-art modification of this repair will be developed by modifying the geometry and boundary conditions of the finite element model for the mechanics of the beating ventricles with LVA. These models will be used to predict the effects of these repairs on three-dimensional myocardial stress and strain distributions. This study will: 1) determine the mechanism underlying the regional mechanical dysfunction associated with LVA; and 2) provide the means to objectively evaluate modifications of conventional aneurysm repair and to develop new operations, possibly based on modifications of cardiomyoplasty or on """"""""heart patches"""""""" produced from myocardial tissue cultures.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL058759-03
Application #
6056448
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1997-09-01
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2001-08-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Guccione, Julius M; Walker, Joseph C; Beitler, Jeremy R et al. (2006) The effect of anteroapical aneurysm plication on end-systolic three-dimensional strain in the sheep: a magnetic resonance imaging tagging study. J Thorac Cardiovasc Surg 131:579-586.e3
Walker, Joseph C; Ratcliffe, Mark B; Zhang, Peng et al. (2005) MRI-based finite-element analysis of left ventricular aneurysm. Am J Physiol Heart Circ Physiol 289:H692-700
Senft, Albert P; Korfhagen, Thomas R; Whitsett, Jeffrey A et al. (2005) Surfactant protein-D regulates soluble CD14 through matrix metalloproteinase-12. J Immunol 174:4953-9
Zhang, Peng; Guccione, Julius M; Nicholas, Susan I et al. (2005) Left ventricular volume and function after endoventricular patch plasty for dyskinetic anteroapical left ventricular aneurysm in sheep. J Thorac Cardiovasc Surg 130:1032-8
Walker, Joseph C; Guccione, Julius M; Jiang, Yi et al. (2005) Helical myofiber orientation after myocardial infarction and left ventricular surgical restoration in sheep. J Thorac Cardiovasc Surg 129:382-90
Guccione, Julius M; Salahieh, Ali; Moonly, Scott M et al. (2003) Myosplint decreases wall stress without depressing function in the failing heart: a finite element model study. Ann Thorac Surg 76:1171-80; discussion 1180
Quarterman, Renee L; Moonly, Scotr; Wallace, Arthur W et al. (2002) A finite element model of left ventricular cellular transplantation in dilated cardiomyopathy. ASAIO J 48:508-13
Guccione, J M; Moonly, S M; Wallace, A W et al. (2001) Residual stress produced by ventricular volume reduction surgery has little effect on ventricular function and mechanics: a finite element model study. J Thorac Cardiovasc Surg 122:592-9
Guccione, J M; Moonly, S M; Moustakidis, P et al. (2001) Mechanism underlying mechanical dysfunction in the border zone of left ventricular aneurysm: a finite element model study. Ann Thorac Surg 71:654-62
Guccione, J M; Motabarzadeh, I; Zahalak, G I (1998) A distribution-moment model of deactivation in cardiac muscle. J Biomech 31:1069-73