The neointimal response to stents eluting tacrolimus from a degradable coating depends on the balance between polymer degradation and drug release.
OBJECTIVE
To study how the balance between tacrolimus elution and polymer degradation from drug-eluting stents (DES) affects neointimal thickening (NIT) in swine coronary arteries.


RESULTS
We assessed a fast-degrading high dose (2 microg/mm2), a slow degrading low dose (1 microg/mm2) or polymer-only coated DES (Pol) versus bare metal stent (BMS). Coronary segments were pre-injured with a balloon/artery ratio of 1.1 to 1.3. Then stents were implanted at that site with a stent/artery ratio of 1.1, with a follow-up period of 5 to 180 days. Histology showed a well endothelialised neointima (82 +/- 1% in high dose DES vs. 93 +/- 8% in BMS) already at five days, without differences in eNOS expression. Morphometry indicated that neointimal thickness in DES was significantly reduced as compared to BMS and Pol at 28 and 90 days. Polymer degradation products induced a distinct inflammatory response which was effectively suppressed in DES. Between 90 and 180 days, however, the slow degrading low-dose stent showed catch-up of NIT.


CONCLUSIONS
Tacrolimus eluted from a biodegradable stent coating can suppress the inflammatory effect of the coating degradation products if the balance between the drug levels and the degradation products is favorable.
van Beusekom
Heleen
H
Cardiology, Erasmus MC, Rotterdam, The Netherlands.
Sorop
Oana
O
Weymaere
Michael
M
Duncker
Dirk
D
van der Giessen
Willem
W
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D020099:Coated Materials, Biocompatible; D003331:Coronary Vessels / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents / Q000009:adverse effects; D004549:Elastin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019344:Lactic Acid; D008670:Metals; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034421:Sus scrofa; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000494:pharmacology*; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D017540:Tunica Media / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014657:Vasculitis / Q000209:etiology / Q000473:pathology*
D020099:Coated Materials, Biocompatible; D007166:Immunosuppressive Agents; D008670:Metals; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004549:Elastin; D052250:Nitric Oxide Synthase Type III; D016559:Tacrolimus