Fracture in drug-eluting stents increases focal intimal hyperplasia in the atherosclerosed rabbit iliac artery.

OBJECTIVES: Drug-eluting stent (DES) strut fracture (SF) is associated with higher incidence of In-stent restenosis (ISR)-return of blockage in a diseased artery post stenting-than seen with bare metal stents (BMS). We hypothesize that concomitance of drug and SF leads to greater neointimal response. BACKGROUND: Controlled release of therapeutic agents, such as sirolimus and its analogs, or paclitaxel from has reduced tissue based DES failure modes compared to BMS. ISR is dramatically reduced and yet the implications of mechanical device failure is magnified. METHODS: Bilateral Xience Everolimus-eluting stents (EES) were implanted in 20 New Zealand White rabbits on normal (n = 7) or high fat (HF)/high cholesterol (HC) (n = 13) diets. Implanted stents were intact or mechanically fractured. Everolimus concentration was as packaged or pre-eluted. After 21 days, stented vessels were explanted, resin embedded, MicroCT scanned, and analyzed histomorphometrically. RESULTS: Fractured EES were associated with significant (P < 0.05) increases in arterial stenosis and neointimal formation and lower lumen-to-artery area ratios compared to intact EES. Hyperlipidemic animals receiving pre-eluted EES revealed no significant difference between intact and fracture groups. CONCLUSIONS: SF increases intimal hyperplasia, post EES implant, and worse with more advanced disease. Pre-eluted groups, reflective of BMS, did not show significant differences, suggesting a synergistic effect of everolimus and mechanical injury, potentially explaining the lack of SF reports for BMS. Here, we report that ISR has a higher incidence with SF in EES, the clinical implication is that patients with SF after DES implantation merit careful follow-up.

Evaluation of high-pressure retrograde coronary venous delivery of FGF-2 protein.

Delivery of angiogenic factors to ischemic myocardium remains a practical challenge. We evaluated the efficiency and efficacy of delivery of fibroblast growth factor-2 (FGF-2) protein via high-pressure retrograde injection into the anterior interventricular vein (AIV) in a porcine model of chronic myocardial ischemia. Labeled FGF-2 protein was delivered to the myocardium of three pigs via the AIV and the left anterior descending (LAD) coronary artery in three others. At 1 hr, the amount of protein in the left ventricle and the LAD region was quantified. Copper stents were implanted in the LAD of 25 pigs, resulting in chronic myocardial ischemia. At 4 weeks, microsphere-derived myocardial blood flow was assessed at rest and during pacing. In eight pigs (AIV FGF), FGF-2 protein (6 microg/kg) was delivered via high-pressure retrograde injection into the AIV. Six pigs (intracoronary FGF) received the same amount of FGF-2 by intracoronary delivery. Five pigs (AIV saline) received a placebo injection into the AIV and six pigs (control) served as controls. Four weeks later, myocardial blood flow was reassessed. At 1 hr, significantly more FGF remained in the left ventricle (1.3 vs. 0.82 microg; P < 0.04) and in the LAD region (1.2 vs. 0.64 microg; P = 0.03) after AIV compared to intracoronary delivery. Four weeks after treatment, resting LAD blood flow (normalized to right ventricular flow) improved slightly in the AIV FGF and intracoronary FGF arms (1.32-1.37 for both; P = 0.11), while it decreased significantly in the AIV saline (1.32-1.23; P = 0.02) and the control arms (1.32-1.19; P = 0.0004). Pacing LAD blood flow decreased significantly in the control arm (1.30-1.23; P < 0.05), but did not change significantly in the other three arms. High-pressure retrograde injection into the AIV may represent an efficient and effective means for delivering angiogenic factors to ischemic myocardium.