Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model.
BACKGROUND
Stent-based delivery of sirolimus (SRL) has shown reduction in neointimal hyperplasia and restenosis. The purpose of this study was to evaluate the chronic vascular response and the expression of cell cycle regulators after SRL-eluting stent implantation in a porcine coronary model.


METHODS
Forty-nine pigs underwent placement of 109 oversized stents (control, n=54, SRL (140 microg/cm(2)), n=55) in the coronary arteries with histologic analysis and Western blot (PCNA, p27(kip1), CD45, MCP-1, IL-2, IL-6, TNF-beta) at 3, 30, 90 or 180 days.


RESULTS
At 3 days, the mean thrombus area was similar for control (0.38+/-0.19 mm(2)) and SRL (0.29+/-0.09 mm(2)) stents. After 30 days, the mean neointimal area was significantly less for the SRL (1.40+/-0.35 mm(2)) versus the control stents (2.94+/-1.28 mm(2), p<0.001). At 90 and 180 days, the mean neointimal area was similar for the SRL (3.03+/-0.92 and 3.34+/-0.99 mm(2)) as compared with control stents (3.45+/-1.09 and 3.65+/-1.23 mm(2)). Western blot analysis demonstrated an increased expression of p27(kip1) in the vessel wall at 90 days for the SRL versus control stents (p=0.05) but with increased levels of PCNA in the SRL as compared with control stents (p=0.003).


CONCLUSIONS
SRL-eluting stents favorably modulate neointimal formation for 30 days in the porcine coronary model. Long-term inhibition of neointimal hyperplasia is not sustained presumably due to delayed cellular proliferation despite increased levels of the cyclin-dependent kinase p27(kip1) in the vessel wall.
Carter
Andrew J
AJ
Providence Heart and Vascular Institute, Providence St. Vincent Medical Center, 9205 SW Barnes Road, Portland, OR 97225-5218, USA. acarter@providence.org
Aggarwal
Meenakshi
M
Kopia
Gregory A
GA
Tio
Fermin
F
Tsao
Philip S
PS
Kolata
Ron
R
Yeung
Alan C
AC
Llanos
Gerald
G
Dooley
John
J
Falotico
Robert
R
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000032:analysis; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control*; D023921:Coronary Stenosis / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D003331:Coronary Vessels; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D023421:Models, Animal; D011108:Polymers; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D020123:Sirolimus / Q000627:therapeutic use*; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D017211:Treatment Failure; D025521:Tumor Suppressor Proteins / Q000032:analysis; D017539:Tunica Intima / Q000737:chemistry / Q000473:pathology
D015415:Biomarkers; D018797:Cell Cycle Proteins; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D011108:Polymers; D018809:Proliferating Cell Nuclear Antigen; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020123:Sirolimus