To accomplish this, we request funds to increase our sample size of phenotyped individuals, which will provide additional power to detect atherosclerosis-susceptibility genes. To date, we have extensively defined cardiovascular traits for 460 Hutterites. If this proposal is funded, we will be able to collect, process, and analyze data from an additional 300 Hutterites during a multi-day research field trip to the Hutterite colonies in Minnesota in the summer of 2009. We are confident that this cumulative dataset will enable us to detect atherosclerosis-related genes in the Hutterites and set the stage to validate our findings in a non-Hutterite population.
The main objective of this proposal is to examine whether ischemic mitral regurgitation can be relieved by injection of a polymer (polyvinyl alcohol-PVA) that has been formulated specifically for this application, into the infarcted myocardium overlying the papillary muscles. Secondary objectives are to test the hypothesis that the polymer reduces MR by the following mechanisms: 1) by acting as a tissue strengthening and bulking agent to repositioning the papillary muscles and 2) injection of a polymer results in improved ventricular mechanics as reinforcement of the akinetic or dyskinetic myocardial wall, leads to improved regional and global mechanics of the remaining myocardium. The application of polymer therapy in order to reverse remodel the ventricle provides a unique opportunity to develop a less invasive and adjustable approach toward this important valvular disorder.
Advances in polymer chemistry have led to a tremendous variety of polymers, that can be selected and modified based on their physical properties and suitability for use in biologic systems. Polyvinyl alcohol (PVA) polymer is highly water-soluble and elicits little or no host biological response when implanted in animals.14-16 For these reasons, PVA polymers are used in a variety of bioical applications including drug delivery, cell encapsulation, artificial tears, contact lenses, and more recently as nerve cuffs.15 Furthermore, PVA polymer can be formulated in situ with physical properties that are adjustable and capable of withstanding the pulsatile loading conditions in the beating heart. PVA can be designed for injection into the myocardium with subsequent crosslinking once injected by modifying PVA concentrations and physical properties so that crosslinking occurs at or near body temperature.
This project will highlight two roles of echocardiography: as a key participating technique for guiding new cardiac therapeutic interventions that are less invasive, such as PVA polymer injection into the beating heart; and as a quantitative approach for studying regional and global ventricular remodeling and its consequences for valvular function.