Inflammation and Delayed Endothelization With Overlapping Drug-Eluting Stents in a Porcine Model of In-Stent Restenosis

Abstract

iffuse, long coronary lesions are associated with an increased rate of restenosis and poor outcome, despite the development of percutaneous coronary intervention (PCI) techniques. [1][2][3] In particular, the implantation of multiple, overlapping, bare metal stents (BMS) has a high restenosis rate. 4,5 Use of drug-eluting stents (DES) results in a significant and sustained suppression of neointimal proliferation, and has greatly attenuated the relationship between stent length and restenosis rate. As a result, a long DES is usually selected for a diffuse coronary lesion, but if a residual segment of the lesion is left uncovered, additional stenting with some overlap is considered to eliminate the risk of a residual stent gap.Thus in the case of a diffuse, long coronary lesion, overlapping DES are used for complete lesion coverage, but there has been concern whether the overlapping DES have the effect of increasing the local drug dose or whether they Circulation Journal Vol.72, March 2008 could result in dose-related side-effects, such as delayed arterial healing and promotion of inflammation, as compared with overlapping BMS. 6 Few histopathological studies have been done on the response to overlapping DES or BMS, and even less so for the overlapping of different DES, such as the sirolimus-eluting stent (SES) or pacletaxel-eluting stent (PES). Therefore, the present study assessed the histopathological response and the effect on neointimal hyperplasia of overlapping DES or BMS in a porcine model of coronary in-stent restenosis (ISR). Methods Animal Study ProtocolThe animal study was approved by the Ethical Committee of the Chonnam National University Hospital. Study animals were female swine weighing 25-35 kg. To decrease the incidence of acute thrombosis after stenting, premedication with aspirin 100 mg and clopidogrel 75 mg/day was given for 7 days before the procedure. On the day of stent implantation, pigs were anesthetized with ketamine (20 mg/kg intramuscularly) and xylazine (2 mg/kg intramuscularly) and maintained on 3 L/min of supplemental oxygen continuously through a mask. After subcutaneous 2% lidocaine was administered at the cut-down site the left carotid artery was surgically exposed, and a 7F sheath was inserted. Continuous hemodynamic and surface electrocardiographic monitoring was maintained throughout the procedure. After 10,000 units of heparin were administered intravenously as a bolus

Evolução temporal da proliferação neointimal após implante de dois tipos de stent farmacológico com polímeros biodegradáveis em modelo porcino: avaliação qualitativa por tomografia de coerência óptica sequencial

“…23,24 Additionally, autopsy studies have identified the presence of bare struts as a more robust morphological predictor for the occurrence of thrombosis in first-generation DES. 25 The present study with sequential OCT, despite not showing bare struts, did provide images that indicate disCussion Several studies in animal models and previous clinical trials showed delayed endothelialisation of DES when compared to BMS, [21][22][23] and observed the frequent presence of struts covered by thin layers of neointimal tissue, with a thickness well below the limits of detection by intracoronary ultrasound. This delayed heterogeneity in the healing process after 28 days.…”

Intriguing Peri-Strut Low-Intensity Area Detected by Optical Coherence Tomography After Coronary Stent Deployment

“…The presence of PLIA might reflect a difference between DES and BMS for arterial healing. 5 According to previous studies, extracellular matrix remodeling plays an essential role in neointimal formation and excessive matrix formation is a determinant of failure of radiation therapy. 6,7 Our findings are in accordance with those reports, showing greater neointimal proliferation in stents with PLIA than in stents without PLIA, for both DES and BMS.…”

Gliotoxin Inhibits Neointimal Hyperplasia after Vascular Injury in Rats

“…Inflammation has been associated with impaired endothelialization or higher restenosis rates after the use or paclitaxel or 32 P-containing stents [58, 59]. Gliotoxin also has direct actions on the endothelium, reducing the expression of NF-ĸB-dependent adhesion molecules and leukocyte adhesion in activated cultured endothelial cells.…”