Heart failure has reached epidemic proportions in the United States and is responsible for nearly 500,000 deaths each year. The majority of heart failure cases is now the result of infarction-induced ventricular remodeling. The lack of a well-established effective treatment has lead to a continually expanding list of medical and surgical options for the palliation of heart failure patients. Unfortunately, the absence of ventricular wall motion or thickening (akinesis) can be misleading. On the other hand, through the power of computational mechanics based on the finite element (FE) method, it is possible to predict with confidence any changes in global LV function (stroke volume versus end-diastolic pressure) and regional mechanics (end-diastolic and end-systolic myofiber stress distributions) when geometric or loading conditions or myocardial material properties (diastolic stiffness and systolic contractility) are changed, thus approaching the objectives of bioengineering and deductive medicine. Broad, Long-Term Objective: Develop an easy-to-use Myocardial Material Property Software Tool (MMPST) that will enable rapid progress in cardiovascular disease research through the ability of FE models to simulate changes in global LV function and regional mechanics due to medical and/or surgical treatment.
Specific Aims : 1. (A) Develop and (B) validate an MMPST that will enable cardiovascular disease researchers to easily measure regional 3-D myocardial material properties. Validation will involve both Monte Carlo simulations and a deformable silicon gel phantom that is well-described by a single material parameter. 2. Use this MMPST to: A. Measure in-vivo regional 3-D myocardial material properties in normal sheep and sheep with an akinetic or dyskinetic myocardial infarct (Ml). Dobutamine will be given to sheep with an akinetic Ml to test our hypothesis that these MIs must contain contracting myocytes. B. Measure ex-vivo regional 3-D myocardial material properties after arresting and isolating the hearts studied in Aim #2A and inflating the LV with our Vivitro servo-pump system. Additionally, biaxial mechanical testing will be performed on excised akinetic and dyskinetic MIs to further validate our MMPST. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL077921-03
Application #
7385153
Study Section
Special Emphasis Panel (ZRG1-CVS-D (51))
Program Officer
Baldwin, Tim
Project Start
2006-04-15
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
3
Fiscal Year
2008
Total Cost
$384,496
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121
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Lee, L C; Kassab, G S; Guccione, J M (2016) Mathematical modeling of cardiac growth and remodeling. Wiley Interdiscip Rev Syst Biol Med 8:211-26
Burkhoff, Daniel; Guccione, Julius (2016) A New Twist on Mitral Regurgitation. JACC Basic Transl Sci 1:203-206

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