Comparative healing response after sirolimus- and paclitaxel-eluting stent implantation in a pig model of restenosis.
OBJECTIVE
We compared local vessel healing and inflammatory responses associated with nonoverlapping sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES).


BACKGROUND
Sirolimus and paclitaxel may have different effects on vascular healing. In the present study, we analyzed the local histologic effects of drug-eluting stents (DES).


METHODS
We placed 43 stents (22 PES and 21 SES) in 16 Yucatan minipigs. Stents were randomly assigned and placed in the left anterior descending, circumflex, or right coronary arteries (one stent per artery), covering a region previously injured by balloon angioplasty.


RESULTS
Histopathologic analysis showed that the distribution of injury scores was similar between the two stent groups, reflecting the homogeneity of coronary injury secondary to balloon overstretch. Electron microscopy showed complete endothelialization in most cases. Incomplete endothelialization was present in 12.5% of PES and almost 20% of SES at 30 days. In the PES group, moderate to severe inflammation was found in eight arteries, whereas only one vessel had moderate inflammation in the SES group. Severe inflammation was observed significantly more often in the PES than in the sirolimus group (P = 0.006). With the PES group, stent struts overlying side branches had a significantly higher frequency of poor endothelialization scores than did stent struts that did not overlay side branches (P = 0.006).


CONCLUSIONS
In this preclinical study in a pig model of in-stent restenosis, implantation of nonoverlapping DES was associated with local inflammatory reactions and decreased endothelial repair. Impaired endothelialization was visualized in the struts overlying side branches.
Silva
Guilherme V
GV
Department of Adult Cardiology, Texas Heart Institute at St Luke's Episcopal Hospital, Houston, Texas, USA.
Fernandes
Marlos R
MR
Madonna
Rosella
R
Clubb
Fred
F
Oliveira
Edie
E
Jimenez-Quevedo
Pilar
P
Branco
Rodrigo
R
Lopez
Javier
J
Angeli
Franca S
FS
Sanz-Ruiz
Ricardo
R
Vaughn
William K
WK
Zheng
Yi
Y
Baimbridge
Fred
F
Canales
John
J
Cardoso
Cristiano O
CO
Assad
Joao A
JA
Falotico
Robert
R
Perin
Emerson C
EC
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D023903:Coronary Restenosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D002317:Cardiovascular Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D017239:Paclitaxel; D020123:Sirolimus