Jaipal Singh

Nobori stent shows less vascular inflammation and early recovery of endothelial function compared with Cypher stent.

OBJECTIVES The current study sought to examine inflammation at the stented segments of Nobori (Terumo Corporation, Tokyo, Japan) and Cypher (Cordis, Miami, Florida) drug-eluting stents (DES), as well as free radical production and endothelial function of the adjacent nonstented segments in a pig coronary model. BACKGROUND Nobori is a novel DES, incorporating a biolimus A9-eluting biodegradable polymer coated only on the abluminal surface of the stent. These unique features may favorably affect inflammation and endothelial function, as compared to the currently marketed DES. Presently, pre-clinical data on direct comparison of the various generations of DES are not available. METHODS A total of 18 DES were implanted in pig coronary arteries and subsequently explanted at 1 month. Stented segments were assessed by angiography and histology. Ex vivo vasomotor function and superoxide production in segments proximal and distal to the stent were determined. The vasoconstriction, endothelial-dependent relaxation, and endothelial-independent relaxation of proximal and distal nonstented segments were measured. RESULTS Histological evaluation revealed lower inflammatory response with Nobori than with Cypher DES. There is trend for lower angiographic percentage diameter stenosis in Nobori versus Cypher groups (p = 0.054). There was increased endothelium-dependent relaxation, decreased endothelin-1-mediated contraction, and less superoxide production in the vessel segments proximal and distal to Nobori versus Cypher stents. CONCLUSIONS Our data show significantly lower inflammatory response in the stented segments, and rapid recovery of endothelial function of peristent segments in the Nobori group compared with Cypher DES group at 1 month in porcine coronary artery model.

NEOINTIMAL TISSUE CLASSIFICATION USING OPTIMAL COHERENCE TOMOGRAPHY AFTER PACLITAXEL-COATING BALLOON TREATMENT IN PIG IN-STENT STENOSIS MODEL

Background: Paclitaxel-coating balloon (PCB) is a promising devise for treatment of in-stent restenosis (ISR). Recently, paclitaxel-eluting stent (PES) implantation has been reported to induce heterogeneous arterial healing as compared to sirolimus-eluting stent in optical coherence tomography (OCT) and angioscopy studies. The aim of this study is to evaluate histopathological indings with OCT and histology after PCB treatment in pig ISR model.

Vascular function of bioabsorbable stented site after complete absorption of the stent

Background: Drug-eluting bioabsorbable stents (DEBSs) represent a new device-based therapy for coronary artery disease. It has been reported that the stented segment becomes re-endothelialized after 1 month and the segments proximal and distal to the stented site are functional at 2 years. In order to examine whether after complete degradation the DEBS site function was similar to the unstented segments, we performed ex vivo vasomotor function studies using pig coronary arteries. Methods: Eighteen months after implantation in the pig coronary arteries, 10 DEBS sites [four left anterior descending (LAD), four right coronary, and two left circumflex arteries] were assessed for vasomotor function using an organ chamber apparatus. They were stimulated with potassium chloride (KCl), prostaglandin2α (PGF), and three concentrations of endothelin-1 (ET). Endothelium-dependant relaxation (EDR) to substance P (SbP; 0.01–100 pM) and endothelium-independent relaxation (EIDR) to sodium nitroprusside (SNP; 0.001–10 μM) were assessed following constriction with PGF. Remaining stent segments were fixed for histologic examination. Results: DEBS sites showed rapid response to low and high concentrations of KCl, PGF, and ET. EIDR showed concentration-dependent relaxation to SNP (13.3±4.3%, 21.3±5.6%, 52.7±7.1%, 85.5±5.4%, and 100±0%). However, there was no EDR to SbP concentration-dependent stimulation. Hematoxylin/eosin and Verhoeff–Masson staining showed evidence of smooth muscle cell (SMC) migration across polymer struts, and formation of a new abluminal layer was observed. There was complete polymer strut degradation, infiltration of inflammatory cells, and minor fibrosis around some DEBS sites. Myocardial degeneration (∼1×1.5 cm) was found in the septum adjacent to the stented LAD sites (n=4). Vessel wall within the stented segment was thicker and the lumen was narrower than in the proximal and distal segments. Conclusion: During DEBS degradation period, medial SMCs migrate to the neointima developing new layers. We have demonstrated for the first time the ex vivo contraction and relaxation responses at DEBS sites to vasoactive agents after complete degradation of the stent. SMCs recovered contractile and relaxing capabilities in this segment but endothelial function was still impaired.

COMPARISON OF VASCULAR INFLAMMATION AND ENDOTHELIAL FUNCTION IN RESPONSE TO A NEW NOBORI AND CYPHER DRUG ELUTING STENTS IN PIG CORONARY ARTERIES

Background: Nobori is a 3rd generation Drug Eluting Stent (DES), designed to include drug eluting biodegradable polymer coated only abluminal side of the stent. The new features may differently impact inflammation and endothelium functions as compared to the currently marketed DES. At the present time, preclinical data on direct comparison of these DESs are not available. In this study, we examined vascular inflammation and endothelial function of the segments adjacent to the stent and histology of stented areas of Nobori and Cypher DES.

1104-189 Enhancement of bone marrow-derived endothelial progenitor cell differentiation by protease-activated receptor-1 activation

Vacular Diase, Hypension, nd Prention mary endpoint of target vessel revascularization (TVR) was reached in 63 (13.9%) patients. Several polymorphisms seem to play a role in the restenotic process. So far we identified an association between interleukin 4 (p=0.026) and three polymorphisms in the adrenergic beta-2 receptor (p=0.064,0.011,0.077) and TVR. Also cytotoxic T-lymphocyteassociated protein 4 seems to be associated with TVR (p=0.032) More genotyping is being performed at this moment. Conclusion: Several polymorphisms seem to play a role in the restenotic process in patients with diabetes mellitus. Interleukin 4, cytotoxic T-lymphocyte-associated protein 4 and adrenergic beta-2 receptor seem to be three important genes in the process of restenosis in diabetics. This can lead to a better risk stratification and to a more tailored therapy for diabetic patients to prevent restenosis after PTCA.