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Platelets. 2019 Apr 11:1-7. doi: 10.1080/09537104.2019.1595564. [Epub ahead of print]

Evaluation of an in vitro coronary stent thrombosis model for preclinical assessment.

Perry-Nguyen D1,2,3, Jung RG1,2,3,4, Labinaz A1,2,5, Duchez AC6, Dewidar O3, Simard T1,2,4,7, Karunakaran D2, Majeed K1,7, Sarathy K1,7, Li R8, Ramirez FD1,7,9, Di Santo P1,2,7,9, Rochman R1,2, So D1,7, Foin N10, Hibbert B1,2,4,7.

Author information

1
a CAPITAL Research Group , University of Ottawa Heart Institute , Ottawa , Ontario , Canada.
2
b Vascular Biology and Experimental Medicine Laboratory , University of Ottawa Heart Institute , Ottawa , Ontario , Canada.
3
c Faculty of Medicine , University of Ottawa , Ottawa , Ontario , Canada.
4
d Department of Cellular and Molecular Medicine , University of Ottawa , Ottawa , Ontario , Canada.
5
e Faculty of Science , University of Ottawa , Ottawa , Ontario , Canada.
6
f Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine , University of Ottawa , Ottawa , Ontario , Canada.
7
g Division of Cardiology , University of Ottawa Heart Institute , Ottawa , Ontario , Canada.
8
h School of Life Sciences and Biotechnology , Shanghai Jiao Tong University , Shanghai , China.
9
i School of Epidemiology and Public Health , University of Ottawa , Ottawa , Ontario , Canada.
10
j National Heart Research Institute Singapore, National Heart Centre Singapore , Singapore.

Abstract

Stent thrombosis remains an infrequent but significant complication following percutaneous coronary intervention. Preclinical models to rapidly screen and validate therapeutic compounds for efficacy are lacking. Herein, we describe a reproducible, high throughput and cost-effective method to evaluate candidate therapeutics and devices for either treatment or propensity to develop stent thrombosis in an in vitro bench-top model. Increasing degree of stent malapposition (0.00 mm, 0.10 mm, 0.25 mm and 0.50 mm) was associated with increasing thrombosis and luminal area occlusion (4.1 ± 0.5%, 6.3 ± 0.5%, 19.7 ± 4.5%, and 92.6 ± 7.4%, p < 0.0001, respectively). Differences in stent design in the form of bare-metal, drug-eluting, and bioresorbable vascular scaffolds demonstrated differences in stent thrombus burden (14.7 ± 3.8% vs. 20.5 ± 3.1% vs. 86.8 ± 5.3%, p < 0.01, respectively). Finally, thrombus burden was significantly reduced when healthy blood samples were incubated with Heparin, ASA/Ticagrelor (DAPT), and Heparin+DAPT compared to control (DMSO) at 4.1 ± 0.6%, 6.9 ± 1.7%, 4.5 ± 1.2%, and 12.1 ± 1.8%, respectively (p < 0.01). The reported model produces high throughput reproducible thrombosis results across a spectrum of antithrombotic agents, stent design, and degrees of apposition. Importantly, performance recapitulates clinical observations of antiplatelet/antithrombotic regimens as well as device and deployment characteristics. Accordingly, this model may serve as a screening tool for candidate therapies in preclinical evaluation.

KEYWORDS:

Antiplatelet agents; methods; optical coherence tomography; percutaneous coronary intervention; stent thrombosis

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