Choon-Sik Jhun

A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm

A non-invasive method for estimating regional myocardial contractility in vivo would be of great value in the design and evaluation of new surgical and medical strategies to treat and/or prevent infarction-induced heart failure. As a first step towards developing such a method, an explicit finite element (FE) model-based formal optimization of regional myocardial contractility in a sheep with left ventricular (LV) aneurysm was performed using tagged magnetic resonance (MR) images and cardiac catheterization pressures. From the tagged MR images, 3-dimensional (3D) myocardial strains, LV volumes and geometry for the animal-specific 3D FE model of the LV were calculated, while the LV pressures provided physiological loading conditions. Active material parameters (T(max_B) and T(max_R)) in the non-infarcted myocardium adjacent to the aneurysm (borderzone) and in myocardium remote from the aneurysm were estimated by minimizing the errors between FE model-predicted and measured systolic strains and LV volumes using the successive response surface method for optimization. The significant depression in optimized T(max_B) relative to T(max_R) was confirmed by direct ex vivo force measurements from skinned fiber preparations. The optimized values of T(max_B) and T(max_R) were not overly sensitive to the passive material parameters specified. The computation time of less than 5 hours associated with our proposed method for estimating regional myocardial contractility in vivo makes it a potentially very useful clinical tool.

Mechanical Properties of Surgical Glues Used in Aortic Root Replacement

BACKGROUND Surgical glues are used in mechanical, stentless bioprosthetic, and homograft aortic root replacements to seal and reinforce anastomotic suture lines. The aortic root normally undergoes substantial physiologic dilation and may be affected by the stiffness of applied sealants. We determined the material properties of four common commercial glues, comparing them with known properties of aortic root replacements. METHODS Samples of BioGlue (CryoLife, Inc, Kennesaw, GA), CoSeal (Baxter Healthcare International, Palo Alto, CA), Tisseel (Baxter Healthcare Corp, Glendale, CA), and Crosseal (OMRIX Biopharmaceuticals, Inc, New York, NY) sealants underwent biaxial tensile testing. A Hookean strain energy function was fit to the stress-strain response of each sample, and the Youngs modulus was obtained for comparison of material stiffness. RESULTS Sealants demonstrate a relatively linear response to loading; mean elastic moduli for BioGlue (3,122.04 +/- 1,639.68 kPa), CoSeal (100.02 +/- 67.60 kPa), Tisseel (102.59 +/- 41.13 kPa), and Crosseal (53.56 +/- 32.59 kPa) varied greatly. CoSeal and Tisseel have no significant difference in stiffness (p = 0.897) while Crosseal is more compliant than Tisseel (p = 0.004) and CoSeal (p = 0.055). BioGlue is stiffer than CoSeal, Tisseel, and Crosseal (p < 0.001). Furthermore, BioGlue is much stiffer than cited properties of Dacron grafts, glutaraldehyde-fixed porcine roots, and human aortic tissue. However, CoSeal and Tisseel are much more compliant than the aortic root conduits. CONCLUSIONS BioGlue is much less compliant than the other sealants studied and materials available for aortic root replacement. A surgeons choice of glue should be determined by stiffness as well as sealant efficacy. Sealants with greater stiffness than aortic root replacement material may restrict normal physiologic dilation and cause anastomotic strictures.

Planar Biaxial Mechanical Behavior of Bioartificial Tissues Possessing Prescribed Fiber Alignment

Though it is widely accepted that fiber alignment has a great influence on the mechanical anisotropy of tissues, a systematic study of the influence of fiber alignment on the macroscopic mechanical behavior by native tissues is precluded due to their predefined microstructure and heterogeneity. Such a study is possible using collagen-based bioartificial tissues that allow for alignment to be prescribed during their fabrication. To generate a systemic variation of strength of fiber alignment, we made cruciform tissue constructs in Teflon molds that had arms of different aspect ratios. We implemented our anisotropic biphasic theory of tissue-equivalent mechanics to simulate the compaction by finite element analysis. Prior to tensile testing, the construct geometry was standardized by cutting test samples with a 1:1 cruciform punch after releasing constructs from the molds. Planar biaxial testing was performed on these samples, after stretching them to their in-mold dimensions to recover in-mold alignment, to observe the macroscopic mechanical response with simultaneous fiber alignment imaging using a polarimetry system. We found that the strength of fiber alignment of the samples prior to release from the molds linearly increased with anisotropy of the mold. In testing after release, modulus ratio (modulus in fiber direction/modulus in normal direction) was greater as the initial strength of fiber alignment increased, that is, as the aspect ratio increased. We also found that the fiber alignment strength and modulus ratio increased in a hyperbolic fashion with stretching for a sample of given aspect ratio.

Comparison of Porcine Pulmonary and Aortic Root Material Properties

BACKGROUND The pulmonary autograft remodels when subjected to systemic pressure and subsequent dilation can lead to reoperation. Inherent material property differences between pulmonary and aortic roots may influence remodeling but are currently unknown. The objective of this study was to determine stiffness across a wide range of strain and compare nonlinear material properties of corresponding regions of native aortic and pulmonary roots. METHODS Tissue samples from porcine aortic and pulmonary roots-sinuses and supravalvular artery distal to the sinotubular junction-were subjected to displacement-controlled equibiaxial stretch testing. Stress-strain data recorded were used to derive strain energy functions for each region. Stiffness from low to high strains at 0.15, 0.3, and 0.5 strain were determined for comparisons. RESULTS Aortic and pulmonary roots exhibited qualitatively similar material properties; both had greater nonlinearity in the sinus than supravalvular artery. The pulmonary artery was significantly more compliant than the ascending aorta both circumferentially and longitudinally throughout the strain range (p < 0.03), except at high strain circumferentially (p = 0.06). However, no differences in stiffness were seen circumferentially or longitudinally between pulmonary and aortic sinuses (p > or = 0.3) until high strain, when the pulmonary sinuses were significantly stiffer (p < 0.05) in both directions. CONCLUSIONS Differences in stiffness between porcine aortic and pulmonary roots are regionally specific, supravalvular artery versus sinus. These regional differences may impact the mode of remodeling to influence late autograft dilation.

Effect of Adjustable Passive Constraint on the Failing Left Ventricle: A Finite-Element Model Study

BACKGROUND Passive constraint is used to prevent left ventricular dilation and subsequent remodeling. However, there has been concern about the effect of passive constraint on diastolic left ventricular chamber stiffness and pump function. This study determined the relationship between constraint, diastolic wall stress, chamber stiffness, and pump function. We tested the hypothesis that passive constraint at 3 mm Hg reduces wall stress with minimal change in pump function. METHODS A three-dimensional finite-element model of the globally dilated left ventricle based on left ventricular dimensions obtained in dogs that had undergone serial intracoronary microsphere injection was created. The model was adjusted to match experimentally observed end-diastolic left ventricular volume and midventricular wall thickness. The experimental results used to create the model were previously reported. A pressure of 3, 5, 7, and 9 mm Hg was applied to the epicardium. Fiber stress, end-diastolic pressure-volume relationship, end-systolic pressure-volume relationship, and the stroke volume-end-diastolic pressure (Starling) relationship were calculated. RESULTS As epicardial constraint pressure increased, fiber stress decreased, the end-diastolic pressure-volume relationship shifted to the left, and the Starling relationship shifted down and to the right. The end-systolic pressure-volume relationship did not change. A constraining pressure of 2.3 mm Hg was associated with a 10% reduction in stroke volume, and mean end-diastolic fiber stress was reduced by 18.3% (inner wall), 15.3% (mid wall), and 14.2% (outer wall). CONCLUSIONS Both stress and cardiac output decrease in a linear fashion as the amount of passive constraint is increased. If the reduction in cardiac output is to be less than 10%, passive constraint should not exceed 2.3 mm Hg. On the other hand, this amount of constraint may be sufficient to reverse eccentric hypertrophy after myocardial infarction.

Effective ventricular unloading by left ventricular assist device varies with stage of heart failure: cardiac simulator study.

Although the use of left ventricular assist devices (LVADs) as a bridge-to-recovery (BTR) has shown promise, clinical success has been limited due to the lack of understanding the timing of implantation, acute/chronic device setting, and explantation. This study investigated the effective ventricular unloading at different heart conditions by using a mock circulatory system (MCS) to provide a tool for pump parameter adjustments. We tested the hypothesis that effective unloading by LVAD at a given speed varies with the stage of heart failure. By using a MCS, systematic depression of cardiac performance was obtained. Five different stages of heart failure from control were achieved by adjusting the pneumatic systolic/diastolic pressure, filling pressure, and systemic resistance. The Heart Mate II® (Thoratec Corp., Pleasanton, CA) was used for volumetric and pressure unloading at different heart conditions over a given LVAD speed. The effective unloading at a given LVAD speed was greater in more depressed heart condition. The rate of unloading over LVAD speed was also greater in more depressed heart condition. In conclusion, to get continuous and optimal cardiac recovery, timely increase in LVAD speed over a period of support is needed while avoiding the akinesis of aortic valve.

Tesla-Based Blood Pump and Its Applications

A continuous flow left ventricular assist device (LVAD) that the Penn State University has developed utilizes Tesla turbomachinery technology. Tesla pumping technology patented by Nikola Tesla in the early 20th century has multiple intriguing characteristics such as simpler manufacturing process, reduced turbulent-related stress, less cavitation due to viscous flow distribution over larger surface areas, and less hemolysis by smooth transition of fluid energy. We successfully tested the 1st version of the Penn State Tesla LVAD [1, 2]. We recently tested the 2nd version of the Tesla pump; to make the pump usable in a wide range of patients, the size of the pump was significantly reduced while trying to avoid any degradation of hemodynamic and hemolytic characteristics.Copyright

Characterization of mechanical behavior of a porcine pulmonary artery strip using a randomized uniaxial stretch and stretch-rate protocol

BackgroundMuch of the experimental work in soft tissue mechanics has been focused on fitting approximate relations for specific tissue types from aggregate data on multiple samples of the tissue. Such relations are needed for modeling applications and have reasonable predictability – especially given the natural variance in specimens. There is, however, much theoretical and experimental work to be done in determining constitutive behaviors for particular specimens and tissues. In so doing, it may be possible to exploit the natural variation in tissue ultrastructure – so to relate ultrastructure composition to tissue behavior. Thus, this study focuses on an experimental method for determining constitutive behaviors and illustrates the method with analysis of a porcine pulmonary artery strip. The method characterizes the elastic part of the response (implicitly in terms of stretch) and the inelastic part in terms of short term stretch history (i.e., stretch-rate) Ht 2, longer term stretch history Ht 1, and time since the start of testing T.MethodsA uniaxial testing protocol with a random stretch and random stretch-rate was developed. The average stress at a particular stretch was chosen as the hyperelastic stress response, and deviation from the mean at this particular stretch is chosen as the inelastic deviation. Multivariable Linear Regression Analysis (MLRA) was utilized to verify if Ht 2, Ht 1, and T are important factors for characterizing the inelastic deviation. For acquiring Ht 2and Ht 1, an integral function type of stretch history was employed with time constants chosen from the relaxation spectrum of an identical size strip from the same tissue with the same orientation. Finally, statistical models that characterize the inelasticity were developed at various, nominal values of stretch, and their predictive capability was examined.ResultsInelastic deviation from hyperelasticity was high (31%) for low stretch and declined significantly with increasing stretch to a nadir of 3.6% for a stretch of 1.7. The inelastic deviation then increased with increasing stretch at the same point in the stress-strain curve where stiffness began to increase strikingly. MLRA showed that T is a major inelastic parameter at low deformation. For moderate and high deformations, Ht 2and Ht 1were dominant.DiscussionA randomized uniaxial testing protocol was applied to a strip of porcine pulmonary artery to characterize the elasticity and inelasticity of a soft tissue. We were successful in determining the elastic response and the factors that gave rise to the inelastic deviation. This investigation seeks methods to better define, phenomenologically, the elastic and inelastic behavior of soft tissues.

Ventricular contractility and compliance measured during axial flow blood pump support: in vitro study.

End-systolic elastance and end-diastolic compliance have been used to quantify systolic and diastolic function of the left ventricle (LV). In this study, the effective end-systolic elastance, (EES )eff , end-systolic volume intercept, (V0 )eff , and end-diastolic compliance of the LV were assessed at various levels of left ventricular assist device (LVAD) support. We tested the hypothesis that (EES )eff and (V0 )eff vary as a function of LVAD speed, while compliance does not change. The Penn State in vitro cardiac simulator was used in two heart conditions (control and heart failure [HF]) with the HeartMate II axial flow LVAD. The LVAD speed was linearly increased from 6000 to 11 000 rpm, with 500-rpm increments. The end-systolic and end-diastolic pressure-volume relationships were estimated at each LVAD speed. Acute LVAD support itself showed pseudo-improvement of ventricular contractility. The (EES )eff and (V0 )eff in HF were found to be dependent on the LVAD speed. The effective compliance for both control and HF was independent of the LVAD speed. Therefore, when examining the time-course cardiac recovery induced by the LVAD support, LV performance should be measured immediately before and after LVAD support while keeping LVAD speed consistent to avoid potential overestimation of long-term cardiac recovery.

In Vivo Left Ventricular Geometry and Boundary Conditions

The first basic biomechanics modeling step outlined in the introductory chapter is to define the geometric configuration. In Chapters 12 and 14 we demonstrate the application of either simple (i.e., axisymmetric truncated ellipsoid) or complex (i.e., fully 3-D) left ventricular (LV) geometric models or finite element (FE) meshes. This chapter is primarily concerned with an instructive review of the methodology we have used to create both types of FE meshes, which relies on the “parametric” meshing software TrueGrid®. Since TrueGrid is rather expensive, Section 1.6 describes the use of free software executables available from the Pacific Northwest National Laboratory. The second basic biomechanics modeling step (determine mechanical properties) is addressed in the next three chapters. The third and fourth basic biomechanics modeling steps (governing equations and boundary conditions) are discussed briefly at the end of this chapter.