Polymer-free cerivastatin-eluting stent shows superior neointimal inhibition with preserved vasomotor function compared to polymer-based paclitaxel-eluting stent in rabbit iliac arteries.
The present study was designed to evaluate vasomotor function and vascular biological responses following a novel non-polymeric cerivastatin-eluting stent (CES) versus polymer-based paclitaxel-eluting stent (PES) in a rabbit iliac artery model. Optimisation of DES components and non-polymeric stents may contribute to vascular healing and beneficial to vasomotor function.



In vitro human aortic and coronary smooth muscle cells (hASMC & hCSMC), as well as endothelial cells (hAEC & hCEC) were cultured. IC50 curves were determined for cerivastatin (CER). In vivo PES (n=6) and CES (n=12) stents were implanted in nine rabbits. Vasomotor function was investigated at 28 days by acetylcholine (ACh) followed by histopathological and histomorphometric analyses. CER was cytotoxic to hASMC and hCSMC (IC50s of 10-6 M and 10-5 M, respectively), although such cytotoxic effects were not observed for hAEC and hCEC at maximal study dose. PES-associated vasodilation response to endothelial-dependent ACh was significantly suppressed at both proximal and distal adjacent arterial segments, as compared to CES. Furthermore, microscopically, neointimal inhibition quantified by the neointimal cross-sectional area (IA) was superior with CES (0.60 + or - 0.27 mm(2)) compared to PES (1.35 + or - 0.16 mm(2); P <0.05). Medial area was smaller for PES (0.3 + or - 0.04 mm(2)) than CES (0.5 + or - 0.03 mm(2), p <0.001). Additionally, significant inflammation and fibrin deposition was clearly evidenced in PES compared to CES (p <0.05).



CER elicits a differential effect on hSMC compared to hEC in vitro. In contrast to PES, a novel bioabsorbable sol-gel coated CES demonstrated effective neointimal inhibition with less vessel wall toxicity accompanied by preservation of vasomotor function in the rabbit iliac model.
Pendyala
Lakshmana
L
Saint Joseph's Translational Research Institute/Saint Joseph's Hospital of Atlanta, GA, USA.
Yin
Xinhua
X
Li
Jinsheng
J
Shinke
Toshiro
T
Xu
Yawei
Y
Chen
Jack P
JP
King
Spencer B
SB
Colley
Kenneth
K
Goodchild
Traci
T
Chronos
Nicolas
N
Hou
Dongming
D
D000800:Angioplasty, Balloon / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007083:Iliac Artery / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D020128:Inhibitory Concentration 50; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000633:toxicity; D011108:Polymers; D011725:Pyridines / Q000008:administration & dosage* / Q000633:toxicity; D011817:Rabbits; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D002317:Cardiovascular Agents; D011108:Polymers; D011725:Pyridines; D014665:Vasodilator Agents; C086276:cerivastatin; D017239:Paclitaxel