Over a million Americans experience a myocardial infarction (heart attack) each year. Following a heart attack, damaged heart muscle cannot regenerate;instead, it is gradually replaced by scar tissue over the course of several weeks. The loss of heart muscle reduces the ability of the heart to pump blood, and in many cases this triggers a gradual decline in heart function and alterations in heart size and shape (remodeling) that ultimately lead to heart failure. Although drugs such as angiotensin converting enzyme (ACE) inhibitors can help reduce post-infarction remodeling, the risk of developing heart failure after surviving a heart attack remains high. Because the mechanical properties of the scar tissue that forms after a heart attack are critical determinants of both heart function and the eventual transition to heart failure, several new therapies under development attempt to modify the mechanical properties of that scar in order to reduce left ventricular (LV) remodeling, improve pump function, or both. Recent computer modeling and experimental studies suggest that infarcts that are very stiff in one direction but relatively soft in others (mechanically anisotropic) should provide the best heart function. This proposal focuses on a novel method to create mechanical anisotropy by surgically reinforcing the infarct. Based on preliminary data showing that anisotropic reinforcement dramatically improves pump function immediately after a heart attack, this project will test the hypothesis that anisotropic reinforcement reduces LV remodeling and functional deterioration over the first 2 months following myocardial infarction in a large animal model. New computational modeling studies will also determine whether infarcts in different locations require different patterns of mechanical reinforcement to optimize LV function.

Public Health Relevance

Over a million Americans experience a myocardial infarction (heart attack) each year. After surviving a heart attack, many patients experience a gradual decline in heart function and alterations in heart size and shape (remodeling) that ultimately lead to heart failure. The goal of this work is to test the ability of an innovative new therapy that improves heart function early after a heart attack to reduce subsequent functional deterioration and remodeling.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL111546-01
Application #
8223807
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Schwartz, Lisa
Project Start
2012-01-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
1
Fiscal Year
2012
Total Cost
$226,626
Indirect Cost
$76,626
Name
University of Virginia
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904