Current Research Projects

Hyaluronan enhanced polymeric heart valve prosthesis

Changes in cardiac biomechanics

All present day prosthetic heart valves suffer from complications. Mechanical heart valves (HVs) require life-long anti-coagulation therapy, while bioprosthetic heart valves based on fixed tissue are plagued with durability, immunogenic and calcification issues. Polymeric heart valves promise to combine the best of the mechanical valves and the best of the bioprosthetic heart valves. Our lab has developed a novel biomaterial, BioPoly, made of engineering polymers that are, at a molecular level, interlocked with hyaluronan (HA, a naturally occurring polysaccharide) to make highly hydrophilic hemocompatible polymer leaflets with the durability of engineered synthetic polymers. Preliminary work has shown that BioPoly leaflets have remarkably reduced thrombogenic potential relative to plain polymer leaflets. Further, we have already demonstrated the feasibility of manufacturing BioPoly leaflets and assembling them into an implantable trileaflet valve. The present R01 study aims to gauge the efficacy of BioPoly as a potential alternative to current heart valve technology by fine tuning material composition and processing to meet the durability and antithrombogenic requirements for heart valve leaflets. Our central hypothesis is: BioPoly HVs offer a viable solution to the drawbacks of both bioprosthetic and mechanical HVs. This is tested in three aims. Aim 1 quantifies heart valve hemodynamic performance and the durability/fatigue characteristics of BioPoly heart valves. Aim 2 focuses on elucidating the effects of leaflet composition and processing on hemocompatibility. Aim 3 focuses on understanding the in vivo hemocompatibility and calcification properties of BioPoly HV.

Investigating the role of blood-induced epigenetic forces on heart development

Changes in cardiac biomechanics

The developing embryonic heart is able to effectively circulate blood long before the formation of chambers and valves. The heart is therefore exposed to blood-induced stresses (e.g. shear stress and pressure) throughout the majority of its development. Mechanical stress on cell membranes can induce complex cell signaling processes which ultimately lead to changes in cell expression and function. Several studies have linked abnormal blood flow dynamics in the early stages of development to the formation of congenital heart defects. The aim of this project is to further investigate the effect of blood flow on heart development using the embryonic zebrafish model. We develop methods for quantifying heart function throughout early development and then compare cases with normal and abnormal blood flow. We can also use these methods to investigate the changing cardiac pumping mechanics throughout development.

Related Publication

  • [1] BM Johnson, DM Garrity, LP Dasi. (2013 ) "Quantifying function in the embryonic heart." Journal of Biomechanical Engineering. Accepted for publication.
  • [2] BM Johnson, DM Garrity, LP Dasi. (2013) "The transitional cardiac pumping mechanics of the embryonic heart." Journal of Cardiovascular Engineering and Technology. Accepted for publication.

Work-Load of the Left-Ventricle During Concomitant Heart Disease

Aortic valve

Current severity indices of heart disease are based on isolated measures and models that do not evaluate the net effects of degradation on the cardiovascular system but rather the consequences of solitary factors alone. Although clinical indices are the most established technique available for determining acceptable thresholds for individual diseases they remain ambiguous at best due to their ability to only generally predict physiological and hemodynamic occurrences. In cases of concomitancy these indices fail completely to markedly diagnose the exigency of afflictions due to the compounded roles they play. However, being a pump, the heart has the distinguished characteristic of being a complete system in and of itself. This gives it the ability to be analyzed as such and therefore to determine the net effects that a disease is inducing on it, most specifically though the measurement of work-load and energy output. To determine the work-load and energy requirements of the left ventricle an in-vitro left heart simulator and synthetic aortic valves were built to model the physiology and patho-physiology of any combination of heart valve disease and hypertension. Raw power output was compared with a normalized power index under various physiological conditions and constraints to determine the exigency of concomitant diseases by evaluating the net energy budget. Findings suggest that raw power is a good indicator for both pure disease and concomitant cases such as stenosis, hypertension, and regurgitation but lacks in determining the level of severity for cases with low cardiac output conditions such as occur during heart failure. Currently the cardiovascular energy dissipation index (CEDI) which takes into account individual patient characteristics is being analyzed as a more accurate representation of the net effects of compounded conditions.

Fluid-structure interaction modeling of the native human aortic valve

Vorticity isosurfaces in the aortic sinus

Aortic valve stenosis is among the most common cardiovascular diseases. Recent studies have shown that there exist strong correlations between leaflet stress − both fluid shear and mechanical − and development of calcific lesions that lead to stenosis. Therefore a complete understanding of valve hemodynamics, specifically within the aortic sinus, and mechanical leaflet stress is critical for further understanding the causes and treatments of this disease. To acquire this knowledge, we are developing a fluid-structure interaction (FSI) model of the aortic valve. Since blood flow affects leaflet motion and leaflet motion in turn affects blood flow, a two-way FSI model is necessary to simultaneously solve for hemodynamic and structural parameters. Validation experiments are also being run via particle image velocimetry (PIV) to verify the accuracy of FSI simulations.

Understanding the small-scale structure of turbulence

Contour Plot

Turbulent flows in nature are inherently anisotropic due to the presence of mean shear as the primary mechanism of turbulent production. While there is a considerable body of literature focused on understanding the small-scale phenomenology of isotropic turbulence, the structure of anisotropic flows is plagued by departures from the notion of local isotropy. We investigate these departures systematically through experiments and dimensional reasoning to physically decifer a generailized (unified) description of the small-scale structure of turbulence applicable in real life anisotropic turbulent flows.

Related Publication

  • [1] Khandakar N Morshed, Subhas K Venayagamoorthy, Lakshmi P Dasi (2013) "Intermittency and local dissipation scales under strong mean shear ". Physics of Fluids , Volume 25, 011701, doi: 10.1063/1.4774039
  • [2] Khandakar N Morshed, Lashmi P Dasi (2013) "Effect of strong anisotropy on the dissipative and non-dissipative regimes of the second order structure function". Experiments in Fluids, Volume 54, Issue 5, DOI: 10.1007/s00348-013-1521-7

System characteristics of the Frank-starling pump

Contour Plot

While the heart as a pump is able to re-model to meet the demands of these altered loading conditions, this capacity is limited with ultimate loss of contractility in a chronic setting. The goal of this research is to understand the system characteristics of the heart using zero-dimensional computational modeling and explore the possibility of determining the coefficient of contractility of the heart muscle indirectly from system responses. A lumped parameter model of the pumping ventricle is constructed utilizing the basic principles of the Frank-Startling law. The coupling of the ventricular pump and systemic circulation generate the waveforms that simulate the cardiac hemodynamics. Research is ongoing to recover force tension parameter of heart muscle from the hemodynamic data obtained in 20 patients with pressure-overload and/or volume-overload conditions. A universal method to calculate the force generation capacity of the heart muscle is crucial towards improving clinical management through better timing for intervention.

The lagrangian blood damage index measure of the b-datum leakage through the bileaflet mechanical heart valve

Implantation of a bileaflet mechanical heart valve (BMHV) continues to be associated with a risk of thromboembolic complications despite anti-coagulation therapy. This has been attributed to the structurally rigid design of the leaflets and valve mechanics combined with an intricate hinge mechanism for the rigid leaflets. The closure mechanics of the leaflets is associated with the formation of the closing vortex as a precursor to the eventual regurgitation jet that emanates from the b-datum line of BMHVs. It may be assumed that the formation of the closing vortex and the subsequent regurgitation jet are governed by the overall magnitude of the driving mean aortic pressure. The aim of this research is to understand the closing dynamics of BMHV leaflets, the formation of the closing vortex and regurgitation jet, and to quantify thromboembolic potential.

In Vitro Beating Heart Simulator for minimally invasive heart valve therapy research

Contour Plot

Heart disease is the number one cause of death today in the United States with aortic valve stenosis (AVS) being a major contributor to the mortality rate. The main treatment for most AVS cases is Aortic Valve Resection or AVR. This method of treatment is extremely invasive and can lead to many complications and have a long term impact on the patient. The objective of this research is to develop an in vitro beating heart simulator which will significantly reduce the time required to develop, test and refine surgical instruments and procedures for use in minimally invasive transapical aortic valve replacement. This system is unique when compared to other similar systems in that it is designed to allow testing of both Transcatheter and Transapical implantation methods and works well for mitral valve and aortic valve studies.

Previous Research Project

Effects of structure on flow mechanics in the human left ventricle and respiratory tract

Contours plot

Cardiac and respiratory dysfunctions are often caused by abnormal flow mechanics due to altered anatomical structure. This structure in the human body is very complex and ranges over many different scales. We investigated the flow patterns in the left ventricle of the heart caused by small scale features called trabeculae as well as fluid dynamics in the respiratory airways due to large-scale anatomy. Fractal geometry was used to help characterize the inner surface of the left ventricle at different times during the cardiac cycle. The fractal dimension of the ventricle was determined using a custom box-counting algorithm developed in MATLAB, and it was shown that trabeculae do indeed play a role in the biomechanics of heart pumping. Computational fluid dynamics (CFD) was also run on the respiratory tracts of three different patients to determine airflow effects due to age and intubation. Three dimensional models were constructed from computed tomography (CT) scans and simulations were run in ANSYS Fluent. Results of the study were validated through grid and time step sensitivity studies as well as comparison to previous studies. It was shown that flow mechanics in the airways of children change with age as well as with the introduction of an intubation tube.