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

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

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

4.  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  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 Clark & Glagov, 1985 Impact of Structure on Biomechanics Kilpatrick, Xu, Vito, Glagov

5. Atherosclerosis & Heterogeneity Virmani et al 2000 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. local biaxial (R,  ) transmural deformation Arterial Biomechanics on Local Scale X Y   displacemt field=f(r,  ) positioner artery chamber CCD

7. 1 (dynes/cm 2 )= 0.1 Pa CONSTITUENT E 1 (dynes/cm 2 ) E 2 (dynes/cm 2 ) oo LIPID ACCUMULATIONS 3.81x10 4 3.88x10 5.182 DISEASE-FREE MEDIA TISSUE 6.15x10 5 2.45x10 6.137 FIBROUS INTIMAL TISSUE 4.83x10 6 1.82x10 7.082 CALCIFIC REGIONS 3.99x10 7 1.07x10 8.053 Assumes incrompressible, isotropic, bilinear elasticity. strain oo stress E2E1E2E1 Kilpatrick-Beattie et al, J. Biomech. Eng., 1998. Tissue Component Mechanical Properties Braunwald E. Disease free media Lipid accumulations Fibrous intima or cap Calcific regions

8. HISTOLOGY L = lipid accumulations H = disease-free F = fibrous intima dynes/cm 2 Biomechanics Reflects Pathology MMP-1 LUMEN SURFACE Kilpatrick et al, J. Mech. Med. Biol., 2002.

9. lipidlipid Stress (dynes/cm 2 ) Strain Energy (dynes/cm 2 ) Can therapeutic strategies be designed to selectively invoke/suppress certain responses? Laplace Histology, Histochemistry, & Biomechanics disease-free media MMP-1MMP-1 fibrous intima Ca ++ Kilpatrick-Beattie et al, J. Biomech. Eng., 1998.

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

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

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

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

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

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

16. Impact of Sy Glagov Braunwald E.