Biomechanics of Heterogeneous Arteries & The Implications for Medical Device R&D

1. Biomechanics of Heterogeneous Arteries& The Implications for Medical Device R&D Hemodynamics & Vascular Remodeling Symposium in Honor of Dr. Seymour Glagov Deborah Kilpatrick, PhD Program Manager New Ventures Group,Guidant Corporation

2. Georgia Tech-University of Chicago Prof. Ray Vito Prof. Sy Glagov

3. Arterial Structure & Function arterial medial structure Clark & Glagov, Arterioscl 1985 arterial remodeling in atherosclerosis Glagov et al, NEJM 1987

4. Clark & Glagov, 1985 Kilpatrick, Xu, Vito, Glagov Impact of Structure on Biomechanics • Complex Constitutive Behavior • nearly incompressible, viscoelastic solid with residual stresses • characteristic soft tissue nonlinearity • Multiaxial, Finite Deformation • up to 100% ii possible • Anisotropy • orientation of ECM proteins, SMC important • Heterogeneity • cellular and ECM composition variable with patient, age, etc., and DISEASE • histology & histochemistry dependent behavior

5. Virmani et al 2000 Atherosclerosis & Heterogeneity • Constitutive laws are different • Deformation behavior changes • Material symmetry is altered • Heterogeneity becomes a BIG issue So, how do we deal with heterogeneity in terms of overall behavior?

6. displacemt field=f(r,) CCD artery chamber Y   positioner X Arterial Biomechanics on Local Scale local biaxial (R,) transmural deformation

7. CONSTITUENT E1 (dynes/cm2) E2 (dynes/cm2) eo 3.81x104 3.88x105 .182 LIPID ACCUMULATIONS • Disease free media • Lipid accumulations • Fibrous intima or cap • Calcific regions DISEASE-FREE MEDIA TISSUE 6.15x105 2.45x106  .137 FIBROUS INTIMAL TISSUE 4.83x106 1.82x107 .082 Assumes incrompressible, isotropic, bilinear elasticity. CALCIFIC REGIONS 3.99x107 1.07x108  .053 E2 E1 stress Braunwald E. eo strain 1 (dynes/cm2)= 0.1 Pa Tissue Component Mechanical Properties Kilpatrick-Beattie et al, J. Biomech. Eng., 1998.

8. HISTOLOGY dynes/cm2 LUMEN SURFACE FI L = lipid accumulations H = disease-free F = fibrous intima MMP-1 LA Biomechanics Reflects Pathology Kilpatrick et al, J. Mech. Med. Biol., 2002.

9. Histology, Histochemistry, & Biomechanics Laplace MMP-1 Ca++ fibrous intima Strain Energy (dynes/cm2) disease-free media lipid Stress (dynes/cm2) Can therapeutic strategies be designed to selectively invoke/suppress certain responses? Kilpatrick-Beattie et al, J. Biomech. Eng., 1998.

10. Impact on Medical Device R&D • What happens at the tissue-device interface? • How could artery/lesion biomechanical behavior drive device design, and vice-versa?

11. Stent Struts Farb, et al, Circ 1999 Clinical Relevance to Coronary PTCI

12. normalized  Tissue-Device Interaction R&D Tissue Mechanical Testing human LAD porcine LAD Device Application Vessel/plaque Modeling Feezor et al, Proc. ASME Summer Bioeng Conf, 2001. Data on file at Guidant.

13. HP SONOSIVUS imaging30 MHz, 30 fps online pressure and temperature monitor pressure control Pressure pump and saline tank access via left main ostium thermal control intact LAD on myocardial bed IVUS catheter environmental chamber The Cleveland Clinic Foundation proximal & local lumen pressure monitor Intact Coronary Biomechanics intact coronary transmural P- deformation Tajaddini et al, J. Biomech. Eng., 2003

14. lipid lipid Biomechanics of PTCI in CAD Feezor et al, 2003 ASME Summer Bioeng Conf, submitted. Model developed at Guidant.

15. fibroatheroma A fibroatheroma B Biomechanics Reflects Pathology (yet again!) Model-Predicted Lesion Shoulder Stress in PTCI Feezor et al, 2003 ASME Summer Bioeng Conf, submitted. Model developed at Guidant. Data on file at Guidant.

16. Braunwald E. Impact of Sy Glagov