Validated model of platelet slip at stenosis and device surfaces

Abstract

Platelets are central to thrombosis. However, it is unknown whether platelets slip at vascular or device surfaces. The presence of platelet slip at a surface would interrupt physical contact between the platelet and that surface, and therefore diminish adhesion and thrombosis. Unfortunately, no existing technology can directly measure platelet slip in a biological environment. The objective of this study was to explore whether microspheres–modeling platelets–slip at different vascular and device surfaces in an acrylic scaled-up model coronary artery. The microspheres (3.12 µm diameter) were suspended in a transparent glycerol/water experimental fluid, which flowed continuously at Reynolds numbers typical of coronary flow (200–400) through the model artery. We placed a series of axisymmetric acrylic stenoses (cross-sectional area reduction [CSAr], 20–90%) into the model artery, both without and with a central cylinder present (modeling a percutaneous interventional guide wire, and with a scaled-up Doppler catheter mounted upstream). We used laser Doppler velocimetry (LDV) to measure microsphere velocities within, proximal and distal to each stenosis, and compared to computer simulations of fluid flow with no-slip. For validation, we replaced the acrylic with paraffin stenoses (more biologically relevant from a surface roughness perspective) and then analyzed the signal recorded by the scaled-up Doppler catheter. Using the LDV, we identified progressive microsphere slip proportional to CSAr inside entrances for stenoses ≥60% and ≥40% without and with cylinder present, respectively. Additionally, microsphere slip occurred universally along the cylinder surface. Computer simulations indicated increased fluid shear rates (velocity gradients) at these particular locations, and logistic regression analysis comparing microsphere slip with fluid shear rate resulted in a c-index of 0.989 at a cut-point fluid shear rate of (10.61 [cm⁻¹]×mean velocity [cm×sec⁻¹]). Moreover, the presence of the cylinder caused disordering of microsphere shear rates distal to higher grade stenoses, indicating a disturbance in their flow. Finally, despite lower precision, the signal recorded by the scaled-up Doppler catheter nonetheless indicated slip at the entry into and at most locations distal to the 90% stenosis. Our validated model establishes proof of concept for platelet slip, and platelet slip explains several important basic and clinical observations. If technological advances allow confirmation in a true biologic environment, then our results will likely influence the development of shear-dependent antiplatelet drugs. Also, adding shear rate information, our results provide a direct experimental fluid dynamic foundation for antiplatelet-focused antithrombotic therapy during coronary interventions directed towards higher grade atherosclerotic stenoses.

Keywords:

• Cardiovascular
• hydrodynamics
• models
• platelet adhesiveness
• shear strength
• thrombosis

Data Availability Statement

All data generated or analyzed in this study are presented in this published article with the exception of the scaled-up Doppler catheter beam power distribution data, which can be viewed as beam power distribution plots in the supplementary information file.

Acknowledgements

The authors wish to express appreciation to B. Pat Denardo (deceased) from the National Aeronautics and Space Administration Ames Research Center (Sunnyvale, CA) for critical advising in the design of the test section, and Professor Lawrence Talbot (deceased) from the College of Engineering at the University of California, Berkeley, for scientific and technical advising in other design aspects and data collection for this research project.

The authors also thank Professor Mark Walters, Director of the Duke University Shared Materials Instrumentation Facility (SMIF), for surface roughness measurements. SMIF is a member of the North Carolina Research Triangle Nanotechnology Network (RTNN), which is supported by the National Science Foundation (Grant ECCS-1542015) as part of the National Nanotechnology Coordinated Infrastructure (NNCI).

Declaration of Interest

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by: American Heart Association [California Affiliate Grant 88-N7]; North Carolina Research Triangle Nanotechnology Network [Kickstarter Program].