1. Sirolimus-Eluting Stent Implantation Aggravates Endothelial Vasomotor Dysfunction in the Infarct-Related Coronary Artery in Patients With Acute MI Journal of the American College of Cardiology Vol. 50, No. 14, 2007

2. Introduction Sirolimus-eluting stent (SES) reduces restenosis compared with bare stents (BS) sirolimus : cell-cycle arrest in the late G1-phase delayed healing of the traumatized vessel wall

3. Indication of long-term endothelial dysfunction after sirolimus-eluting stent implantation European Heart Journal (2006) 27, 166–170 local epicardial endothelial function 6 months after sirolimus-eluting stent (SES) or bare metal stent (BS) implantation  endothelial-dependent and -independent vasomotion

4. Mean coronary segment diameter change Achetylcoline : endothelium-dependent vasomotion Nitrates : endothelium-independent vasodilation Achetylcoline : endothelium-dependent vasomotion Nitrates : endothelium-independent vasodilation Reduction Dilatation

6. Mean coronary artery segment luminal diameter change after intracoronary infusion of acetylcholine with incremental concentrations 10 -8 10 -7 10 -6 Mean coronary artery segment luminal diameter change after intracoronary infusion of acetylcholine with incremental concentrations 10 -8 10 -7 10 -6 -21% (-26; -8) vs. -8% (-13; -7)

7. Endothelial damage during reperfusion injury after MI the restoration of blood flow to ischemic myocardium infarct extension and poor prognosis after AMI Vascular endothelial growth factor (VEGF) endothelial repair and microvessel growth sirolimus is capable of reducing expression of VEGF Aim sirolimus eluting stent impair the recovery of reperfusion-induced endothelial injury entirely in the infarct related coronary artery beyond the distal edge of the SES early after AMI

8. First AMI due to occlusion of a proximal LAD First AMI due to occlusion of a proximal LAD

10. Response of epicardial coronary vasomotor and coronary blood flow  Ach infusion after 2 weeks CBF : coronary blood flow

11. Comparisons of Coronary Vasomotor Responses to isosorbide dinitrates or sodium nitroprusside Response to isosorbide dinitrates Response to sodium nitroprusside Epithelium –independent ~

12. VEGF Levels in the Plasma AO : aortic root AIV : ant. Interventricular vei n AO : aortic root AIV : ant. Interventricular vei n > =

13. Differential Effects of Drug-Eluting Stents on Local Endothelium-Dependent Coronary Vasomotion Journal of the American College of Cardiology Vol. 51, No. 22, 2008

14. New DES have been developed Nobori (Terumo Corporation, Tokyo, Japan) second-generation DES bioresorbable polymer (polylactic acid) from which biolimus A9, an analogue of sirolimus, is eluted Aim Endothelium dependent and -independent coronary vasomotion after 9 months after either biolimus A9-eluting stent (BES) or SES implantation, using right atrial pacing at increasing rate steps

15. Cardiac pacing  increases myocardial oxygen requirements  augmented coronary blood flow  dilates human coronary picardial arteries But …. Endothelial cell dysfunction  reduced nitric oxide activity  paradoxical constriction of epicardial arteries wi

16. BES biolimus A9-eluting stent(s) SES sirolimus-eluting stent(s)

18. SES BES

19. SES

20. Conclusion SES implantation may have an adverse effect on local endothelium-dependent vasomotor responses compared with BS implantation During the course of AMI, SES implantation adversely affects endothelium-dependent vasomotor function after the ischemia reperfusion  reduction in myocardial VEGF secretion Endothelium-dependent vasomotion at adjacent stent segments seems to be preserved after BES implantation  different drug release kinetics, DES design, or characteristics of polymer used in the stent system