Long-term vascular responses to Resolute® and Xience V® polymer-based drug-eluting stents in a rabbit model of atherosclerosis.

OBJECTIVES: To assess the late postinterventional response to iliac stenting in atheromatous rabbits using the Xience V everolimus-eluting stent (Xience V EES; Abbott Vascular) and the Resolute zotarolimus-eluting stent (Resolute ZES; Medtronic Vascular) with the MultiLink Vision bare metal stent (BMS; Abbott Vascular) as a reference. BACKGROUND: Xience V EES and Resolute ZES were developed to overcome shortcomings of first-generation DES. METHODS: Functional and microscopic changes were assessed by organ bath experiments and histopathologic examination. Gene expression was investigated using RT-PCR. RESULTS: After 91 days, re-endothelialization was nearly complete (BMS: 93 ± 3%; Resolute ZES: 92 ± 2%; Xience V EES: 94 ± 3%; P = 0.10). Neointima thickness was similar in Resolute ZES (0.17 ± 0.08 mm) and BMS (0.17 ± 0.09 mm), and reduced in Xience V EES (0.03 ± 0.01 mm; P < 0.0001). Xience V EES had less peri-strut inflammation compared with BMS (P = 0.001) and Resolute ZES (P = 0.0001), while arterial segments distal to Xience V EES were more sensitive to acetylcholine than those distal to BMS and Resolute ZES (P = 0.02). Lectin-like oxidized receptor-1 was overexpressed in stented arteries (P < 0.001), whereas thrombomodulin was downregulated in Resolute ZES (P = 0.01) and BMS (P = 0.02) compared to unstented arteries of rabbits on regular chow. No significant changes were seen for vascular cell adhesion molecule-1, nitric oxide synthase 3, or endothelin-1. CONCLUSIONS: At 3-month follow-up, nearly complete re-endothelialization was achieved for all stent groups. Xience V EES induced greater suppression of neointimal growth and peri-strut inflammation, higher vasorelaxation to acetylcholine, and expression of thrombomodulin at the level of unstented controls.

Isolation of high-quality RNA from stented blood vessels.

Stents have become a standard of care for the treatment of coronary artery disease. A series of cellular and molecular processes contribute to the vascular response following stent placement. For the purpose of local gene expression studies, metallic stent struts are usually removed from the vessel wall with forceps under a dissection microscope prior to RNA extraction. Main drawbacks of the manual dissection are that it may cause additional tissue damage and compromise the quality of RNA through prolonged tissue handling. In this technical note, we report the recovery of high-quality RNA from atherosclerotic vessels with stent struts left in situ.

Resolute and Xience V polymer-based drug-eluting stents compared in an atherosclerotic rabbit double injury model.

AIM: To evaluate differences in strut coverage, inflammation and endothelialization between two second-generation polymer-based drug-eluting stents (DES) in an atherosclerotic rabbit double-injury iliac artery model at 28 days follow-up. METHODS AND RESULTS: Rabbits with induced atheroma received bilateral iliac artery stents: everolimus-eluting stent (Xience V EES; Abbott Vascular), zotarolimus-eluting stent (Resolute ZES; Medtronic CardioVascular), or bare-metal stent (BMS; MultiLink Vision; Abbott Vascular). After 28 days, total neointimal coverage examined by scanning electron microscopy was >98% for all three stent types. Neointimal thickness above stent struts was decreased by 50% in Xience V EES (0.06 ± 0.01 mm; P = 0.00001) compared with BMS (0.15 ± 0.03 mm) and Resolute ZES (0.12 ± 0.04 mm). Luminal area was largest for Xience V EES (3.79 ± 0.33 mm(2) ; P = 0.0003 for Xience V EES vs. BMS), followed by Resolute ZES (3.46 ± 0.45 mm(2) ; P = 0.083 for Resolute ZES vs. BMS) and BMS (3.07 ± 0.53 mm(2) ). Percentage area stenosis was smallest for Xience V EES (17.23 ± 3.64%; P = 0.00001), while BMS (30.25 ± 7.48%) and Resolute ZES (30.79 ± 7.15%) did not differ. Endothelial monolayer regrowth was significantly lower in Resolute ZES (65 ± 13%) versus BMS (79 ± 11%; P = 0.004). There was no difference between Xience V EES (74 ± 10%) and BMS. Xience V EES was further associated with a lower number of inflammatory cells surrounding the stent struts (7 ± 2 per strut) in comparison to Resolute ZES (15 ± 6; P = 0.0001) and BMS (17 ± 9; P = 0.0005). CONCLUSION: In this atherosclerotic rabbit model, Xience V EES suppressed neointimal thickening better, with normal endothelial regrowth as compared with BMS, and less strut-induced inflammation.

New-generation drug-eluting stents: focus on Xience V® everolimus-eluting stent and Resolute® zotarolimus-eluting stent.

Compared to bare metal stent angioplasty, first-generation drug-eluting stents (DES) have markedly reduced the incidence of in-stent restenosis. However, given the increased concerns over late and very late stent thrombosis, newer-generation DES were developed. To date, these DES have virtually replaced the use of first-generation DES worldwide. In this review article, we carefully consider the pre-clinical and clinical trials that have been performed with currently available, european conformity-marked and Food and Drug Administration-approved new-generation Resolute(®) and Xience V(®) DES.

Automatic assessment of stent neointimal coverage by intravascular optical coherence tomography.

AIMS: This study aimed to validate automatic intravascular optical coherence tomography (IVOCT) analysis for the evaluation of neointimal coverage in response to stent implantation. METHODS AND RESULTS: Fourteen stented segments in common iliac arteries, acquired from a total of seven adult male New Zealand White rabbits, were interrogated in vivo by IVOCT. Durable polymer everolimus-eluting stents (EES; Xience V, Abbott Vascular, Santa Clara, CA, USA) were used exclusively. Comparison with histology was made in a total of 63 pairs of images, where neointimal thickness over corresponding individual stent struts was assessed. A high correlation coefficient (R = 0.85, P < 0.001) was obtained by comparing automatic IVOCT analysis with histology. Moreover, Bland-Altman statistics showed good limits of agreement (LOAs) of ±45 µm, with an average difference of -10 µm. In addition, manual IVOCT assessment presented very similar results when compared with histology (R = 0.83, P < 0.001 and LOA = ±48 µm with an average difference of -8 µm). Therefore, a very high correlation value was found, comparing manual to automatic IVOCT measurements (R = 0.95, P < 0.001) together with good LOAs (±27 µm) and an average difference of -2 µm. CONCLUSION: The results of the study suggest that automatic IVOCT analysis is a reliable and accurate tool able to speed up current IVOCT analysis procedures. This would potentially allow for a better integration of IVOCT in clinical practice and clinical studies assessing vascular response to stent implantation in a large series of patients.