1. Evaluation of an in vitro coronary stent thrombosis model for preclinical assessment.
- Author
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Perry-Nguyen, Dylan, Jung, Richard G., Labinaz, Alisha, Duchez, Anne-Claire, Dewidar, Omar, Simard, Trevor, Karunakaran, Denuja, Majeed, Kamran, Sarathy, Kiran, Li, Ruonan, Ramirez, F. Daniel, Di Santo, Pietro, Rochman, Rebecca, So, Derek, Foin, Nicolas, and Hibbert, Benjamin
- Subjects
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CORONARY disease , *ANIMAL models in research , *BIOABSORBABLE implants , *DRUG-eluting stents , *PERCUTANEOUS coronary intervention , *ANTICOAGULANTS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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