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1 What Interventional Cardiology Has Taught Us About Physiology and Pathophysiology 47 th Annual Carl J. Wiggers Memorial Lecture Cleveland, OH David R. Holmes, MD Mayo Clinic Rochester, MN Presenter Disclosure Information David R. Holmes, Jr., M.D. What Interventional Cardiology Has Taught Us About Physiology and Pathophysiology The following relationships exist related to this presentation: None Interventional Cardiology Physiology and Pathophysiology Acute ischemic syndromes Coronary flow Role of platelets in health and disease Vascular healing 1

2 Endothelial Function Basic Science to Clinical Practice Discovery of and the role of the endothelium 198 Basic science Clinical CP CP CP

3 3 CP CP CP8137-5

4 CP Dependent Relaxation Responses Relaxation (% contraction to norepinephrine) Saphenous Veins Without endothelium (n=9) With endothelium (n=22) Lüscher et al: JM 319:462, (-logm) Internal Mammary Arteries 8 7 Without endothelium (n=9) With endothelium (n=27) (-logm) CP Discovery of and the role of the endothelium Endothelial Function Basic Science to Clinical Practice First function in humans Basic science Clinical CP

5 New England Journal of medicine 315 (17) 1986 CP C1 1-9 M Ach 1-8 M Ach TNG New England Journal of medicine 315 (17) 1986 CP Endothelial Function Basic Science to Clinical Practice Discovery of and the role of the endothelium Endothelial function with exercise and mental stress First function in humans Basic science Clinical CP

6 Exercise and Coronary Endothelial Function 14 Dilates with Ach Vessel diameter (% control) Gordon, Control Ach 1-6 M Exercise CP Exercise and Coronary Endothelial Function 14 Dilates with Ach Constricts with Ach Vessel diameter (% control) Gordon, Control Ach 1-6 M Exercise CP Discovery of and the role of the endothelium Endothelial Function Basic Science to Clinical Practice Endothelial function with exercise and mental stress Comparison peripheral and coronary function Endothelial function and myocardial ischemia First function in humans Noninvasive function Coronary function in clinical Basic science Clinical 6

7 Coronary Blood Flow Function Protocol Diagnostic angiography Adenosine IC µg Endothelial Ach 1-6 Ach 1-5 Ach 1-4 NTG Hemodynamic data Doppler velocity Diagnostic angiogram IVUS Infusion catheter Doppler wire CP Functional Coronary Angiogram Diagnostic angiography Adenosine IC µg Ach 1-6 Ach 1-5 Ach 1-4 NTG Hemodynamic data Doppler velocity Diagnostic angiogram IVUS Infusion catheter Doppler wire CP Functional Coronary Angiogram Diagnostic angiography Adenosine IC µg Ach 1-6 Ach 1-5 Ach 1-4 NTG Hemodynamic data Doppler velocity Diagnostic angiogram IVUS Infusion catheter Doppler wire CP

8 CP Coronary Endothelial Function Protocol Diagnostic angiography Adenosine IC NTG Hemodynamic data Infusion catheter Doppler wire CP The Association Between Non-invasive Tests and Coronary Flow Reserve 2 Endothelial function 4. Non- CFR Change (%) 15 5 Ratio Negative Cessar and Lerman: Cir Int Positive Negative Imaging stress tests Positive CP

9 CP % Percent of CBF in Response to ACH Controls ALVD Prasad and Lerman et al: AHJ, 23 CFR CFR in Response to Adenosine Controls ALVD CP CP

10 Discovery of and the role of the endothelium Endothelial Function Basic Science to Clinical Practice Endothelial function with exercise and mental stress Comparison peripheral and coronary function Endothelial function and myocardial ischemia First function in humans Noninvasive function Coronary function in clinical Association between function and CV events Basic science Clinical CP CP CV Events During Follow-Up (53 Months) 24 2 P<.1 Forearm blood flow (ml/ ml/min) No events Events Heitzer et al: Circulation 14, 21 ACh-induced vasodilation CP

11 Endothelial Dysfunction and CV Events: Meta-analysis of 15 Studies Coronary (N=5) Brachial (N=1) Overall Risk Ratio Lerman and Zeiher Circulation 24 CP the relationship between dysfunction and clinical course after AMI CP Kaplan-Meier Curves for MACE-Free Survival 1. MACEfree survival ACh negative ACh positive.2 P= Months CP

12 12

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