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

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.

• Authors: Dylan Perry-Nguyen, Richard G Jung, Alisha Labinaz, Anne-Claire Duchez, Omar Dewidar, Trevor Simard, Denuja Karunakaran, Kamran Majeed, Kiran Sarathy, Ruonan Li, F Daniel Ramirez, Pietro Di Santo, Rebecca Rochman, Derek So, Nicolas Foin, Benjamin Hibbert
• Journal: Platelets (Platelets) Vol. 31 Issue 2 Pg. 167-173 ( 2020) ISSN: 1369-1635 [Electronic] England
• PMID: 30973035 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Enzymes
• Platelet Aggregation Inhibitors

Topics

• Blood Physiological Phenomena (drug effects)
• Coronary Thrombosis (complications, diagnostic imaging, enzymology, etiology)
• Drug-Eluting Stents (adverse effects)
• Enzymes (blood)
• Humans
• In Vitro Techniques
• Models, Biological
• Percutaneous Coronary Intervention (adverse effects)
• Platelet Aggregation Inhibitors (therapeutic use)
• Stents (adverse effects)
• Thrombosis (blood, complications, enzymology)
• Tomography, Optical Coherence