Coronary bare metal stent implantation in homozygous LDL receptor deficient swine induces a neointimal formation pattern similar to humans.
BACKGROUND
To date, most of all new developments in stent technologies are tested in normal animals. Although invaluable in the evaluation of device safety, the juvenile domestic swine (DS) do not follow the biological healing response occurring in humans following coronary stent implantation. By using a novel swine breed afflicted with familial hypercholesterolemia (FHS), we aimed to analyse the vascular response occurring following bare metal stent (BMS) implantation by comparing in vivo endovascular imaging and histological data.


METHODS
A total of 26 swine were included in this study (12 FHS and 14 DS). Sixty eight BMS (FHS=28 versus DS=40) were implanted using a 10% overstretch ratio. Imaging evaluation (IVUS and OCT) was conducted in all animals at 30 (n=14) or 90 (n=12) days following stent implantation. After imaging, the stented coronary segments were harvested for histological evaluation.


RESULTS
At 30 days, the degree of neointimal formation analysed by OCT (%AS=DS 21.9 ± 10% versus FHS 25.4 ± 12%; p=0.18) and histology (DS 24.6 ± 10% versus FHS 23.58 ± 10%; p=0.8) was similar between both animal groups. At 90 days, the degree of neointimal formation in the DS group decreased in all analysed variables (-40% in IVUS neointimal volume, -57% in OCT %AS, and -30% in %AS by histology) compared to the progression of neointimal formation observed in the FHS group (+29% in IVUS neointimal volume, +27% in OCT %AS and +43% in %AS by histology).


CONCLUSIONS
The pattern of neointimal formation following BMS implantation in the FHS follows a progressive course that does not occur in the DS. Therefore, by providing a progressive neointimal biological response to BMS implantation, the FHS could serve as an ideal efficacy model for the validation of drug eluting stent technologies.
Skirball Center for Cardiovascular Research for Cardiovascular Research Foundation, 8 Corporate Dr., Orangeburg, New York, NY 10965, USA.
Armando
A
Tellez
Christian G
CG
Krueger
Paul
P
Seifert
Dawn
D
Winsor-Hines
Cristian
C
Piedrahita
Yanping
Y
Cheng
Krzysztof
K
Milewski
Michael S
MS
Aboodi
Genghua
G
Yi
Jennifer C
JC
McGregor
Tom
T
Crenshaw
Jess D
JD
Reed
Barbara
B
Huibregtse
Greg L
GL
Kaluza
Juan F
JF
Granada
D000818:Animals; D023903:Coronary Restenosis / Q000473:pathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology; D004195:Disease Models, Animal; D006938:Hyperlipoproteinemia Type II / Q000473:pathology* / Q000628:therapy*; D008297:Male; D011973:Receptors, LDL / Q000172:deficiency*; D015607:Stents / Q000662:veterinary*; D013552:Swine; D041623:Tomography, Optical Coherence; D017539:Tunica Intima / Q000473:pathology*; D014463:Ultrasonography
D011973:Receptors, LDL