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Obstructive coronary artery disease is usually treated with drug eluting stents (DES) to restore blood flow. DES successfully reduce scar tissue and restenosis but were long thought to delay re-endothelialization. The latter is thought to be a leading cause for acute stent thrombosis. Understanding early re-endothelialization is essential to improve DES efficacy. One such factor is early thrombus coverage as the interface between stent strut and endothelium, and as such a substrate for re-endothelialization. We therefore investigated parameters associated with early re-endothelialization such as effective stent placement (e.g. malapposition, vascular injury) and thrombus (composition, thickness), in a clinically relevant swine coronary injury model mimicking predilation prior to coronary stenting. We hypothesize that thrombus composition, and parameters of effective stent placement, both affect re-endothelialization.
Each artery (n=24, 8 swine) was predilated 3 times with 30% oversized balloons under guidance of quantitative coronary angiography. Then bare metal stents (BMS) and DES were implanted with 10% oversizing according to a predetermined random scheme. All animals received heparin, clopidogrel and aspirin prior to and during FU. At 3 days, animals were euthanized by a barbiturate overdose and tissues were prepared for histology. Linear regression for re-endothelialization was performed, with balloon injury, stent artery ratio, stent malapposition, thrombus- composition and -thickness as independent parameters. P-values< 0.05 were considered statistically significant.
Regression analysis (ANOVA p=0.001, adjusted R2=0.5) revealed a negative association between malapposition and re-endothelialization (p= 0.007) and a positive association with thrombus thickness (p= 0.03) and erythrocyte content (p=0.004). Stent type (i.e. DES or BMS) did not correlate with re-endothelialization (p=0.7). Beneficial flow patterns, surface characteristics and metabolic aspects of erythrocyte rich thrombi are thought to explain these findings.
Thrombus composition and malapposition following coronary stent implantation independently affect early re-endothelialization. DES did not affect re-endothelialization in this model.
CORONARY: Stents: Drug-Eluting