This Article Full Text Full Text (PDF) All Versions of this Article: 119/15/2078    most recent CIRCULATIONAHA.107.737734v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lee, K.-J. Articles by Benson, L. N. Search for Related Content PubMed PubMed Citation Articles by Lee, K.-J. Articles by Benson, L. N. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Animal models of human disease Smooth muscle proliferation and differentiation Catheter-based coronary and valvular interventions: other Catheter-based coronary interventions: stents Related Article

(Circulation. 2009;119:2078-2085.)
© 2009 American Heart Association, Inc.

Interventional Cardiology

Rapamycin-Eluting Stents in the Arterial Duct

Experimental Observations in the Pig Model

Kyong-Jin Lee, MD, FRCP(C); Aleksander Hinek, MD, PhD, DSc; Rajiv R. Chaturvedi, MRCP(UK), MD, PhD; Claudia L. Almeida, MD; Osami Honjo, MD, PhD; Gideon Koren, MD, FRCP(C), FABMT; Leland N. Benson, MD, FRCP(C)

From the Labatt Family Heart Centre (K.-J.L., R.R.C., C.L.A., O.H., L.N.B.), Divisions of Cardiovascular Research (A.H.) and Pharmacology/Toxicology (G.K.), The Hospital for Sick Children, University of Toronto School of Medicine, Toronto, Ontario, Canada.

Correspondence to Dr Kyong-Jin Lee, The Hospital for Sick Children, 555 University Ave, Toronto, Canada M5G 1X8. E-mail kyong-jin.lee{at}sickkids.ca

Received August 30, 2007; accepted February 13, 2009.

Background— Maintaining arterial duct patency by stent implantation may be advantageous in congenital heart disease management algorithms. Rapamycin, an immunosuppressant drug that demonstrates antiproliferative properties and inhibits smooth muscle cell migration, may deter the intimal hyperplasia that occurs during spontaneous closure and after-stent implantation of the arterial duct.

Methods and Results— Twenty-eight Yorkshire piglets (7 to 11 days old; weight, 2.2 to 4.9 kg) underwent stent implantation of the arterial duct (rapamycin-eluting (n=14) or bare metal (n=14) stents, 3.5-mm diameter) and were euthanized at 2, 4, and 6 weeks. Dissected arterial ducts were analyzed for lumen diameter, smooth muscle cell, and extracellular matrix components. Isolated arterial duct–derived smooth muscle cells were cultured in the presence or absence of rapamycin. Cellular proliferation rates were assessed by Ki-67 detection and [³H]-thymidine incorporation. No significant neointimal proliferation was present in either stent type at 2 weeks. At 4 weeks, the median luminal diameters of the bare metal stents were 87% (P=0.009), 54% (P=0.004), and 77% (P=0.004) that of the drug-eluting stents at the middle and aortic and pulmonary artery ends, respectively. At 6 weeks, the median luminal diameters of the bare metal stents were 0% (P=0.18), 5% (P=0.25), and 61% (P=0.13) that of the drug-eluting stents at the same respective levels. Complete histological occlusion was found in at least 1 level of the lumen in 9 pigs: 1 (17%) in the BMS group at 4 weeks, 5 (83%) in the BMS group at 6 weeks, and 3 (50%) in the DES group at 6 weeks. In vitro studies demonstrated 50%-lower proliferation rates in rapamycin-treated cultures of duct-derived smooth muscle cell cultures (P<0.001).

Conclusions— Rapamycin has antiproliferative actions on the arterial duct. Drug-eluting stents may be a more efficient tool than current palliative options for maintaining patency in critically duct-dependent states, but there may be a finite time-related benefit.

---

 

CLINICAL PERSPECTIVE

Related Article:

Clinical Summaries
Circulation 2009 119: 2017-2019. [Extract] [Full Text]