Potential fluid mechanic pathways of platelet activation

Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here, we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport.

[1]  Arnan Mitchell,et al.  A shear gradient–dependent platelet aggregation mechanism drives thrombus formation , 2009, Nature Medicine.

[2]  J. Riley,et al.  Equation of motion for a small rigid sphere in a nonuniform flow , 1983 .

[3]  Jerrold E. Marsden,et al.  Lagrangian coherent structures in n-dimensional systems , 2007 .

[4]  Alberto Redaelli,et al.  Platelet Activation Due to Hemodynamic Shear Stresses: Damage Accumulation Model and Comparison to In Vitro Measurements , 2008, ASAIO journal.

[5]  G. Haller,et al.  Lagrangian coherent structures and mixing in two-dimensional turbulence , 2000 .

[6]  G. Haller Finding finite-time invariant manifolds in two-dimensional velocity fields. , 2000, Chaos.

[7]  Danny Bluestein,et al.  Flow-induced platelet activation and damage accumulation in a mechanical heart valve: numerical studies. , 2007, Artificial organs.

[8]  G. Hulbert,et al.  A generalized-α method for integrating the filtered Navier–Stokes equations with a stabilized finite element method , 2000 .

[9]  Y. Cho,et al.  Effects of the non-Newtonian viscosity of blood on flows in a diseased arterial vessel. Part 1: Steady flows. , 1991, Biorheology.

[10]  T. Hughes,et al.  A multi-element group preconditioned GMRES algorithm for nonsymmetric systems arising in finite element analysis , 1989 .

[11]  J.,et al.  Whitaker Lecture : Biorheology in Thrombosis Research , 2022 .

[12]  K. Sakariassen,et al.  A perfusion chamber developed to investigate thrombus formation and shear profiles in flowing native human blood at the apex of well-defined stenoses. , 1994, Arteriosclerosis and Thrombosis A Journal of Vascular Biology.

[13]  Danny Bluestein,et al.  Fluid mechanics of arterial stenosis: Relationship to the development of mural thrombus , 1997, Annals of Biomedical Engineering.

[14]  T. Giorgio,et al.  The effects of elongational stress exposure on the activation and aggregation of blood platelets. , 1991, Biorheology.

[15]  L Zuckerman,et al.  Shear-induced activation of platelets. , 1979, Journal of biomechanics.

[16]  Charles A. Taylor,et al.  Characterization of Coherent Structures in the Cardiovascular System , 2008, Annals of Biomedical Engineering.

[17]  Jeanette P. Schmidt,et al.  The Simbios National Center: Systems Biology in Motion , 2008, Proceedings of the IEEE.

[18]  D. Ingber,et al.  Mechanotransduction across the cell surface and through the cytoskeleton , 1993 .

[19]  J. D. Hellums,et al.  1993 Whitaker lecture: Biorheology in thrombosis research , 1994, Annals of Biomedical Engineering.

[20]  D. F. Young,et al.  Flow characteristics in models of arterial stenoses. I. Steady flow. , 1973, Journal of biomechanics.

[21]  A. Crisanti,et al.  Predictability in the large: an extension of the concept of Lyapunov exponent , 1996, chao-dyn/9606014.

[22]  Thomas J. R. Hughes,et al.  Finite element modeling of blood flow in arteries , 1998 .

[23]  Giles R Cokelet,et al.  The rheology of human blood , 1963 .

[24]  J. Marsden,et al.  Definition and properties of Lagrangian coherent structures from finite-time Lyapunov exponents in two-dimensional aperiodic flows , 2005 .

[25]  D. Rubenstein,et al.  Quantifying the effects of shear stress and shear exposure duration regulation on flow induced platelet activation and aggregation , 2010, Journal of Thrombosis and Thrombolysis.

[26]  J. Marsden,et al.  Lagrangian analysis of fluid transport in empirical vortex ring flows , 2006 .

[27]  M. Anliker,et al.  Biomechanics Its Foundations And Objectives , 1972 .

[28]  Roman O. Grigoriev,et al.  Transport and Mixing in Laminar Flows: From Microfluidics to Oceanic Currents , 1994 .

[29]  D. F. Young,et al.  Flow characteristics in models of arterial stenoses. II. Unsteady flow. , 1973, Journal of biomechanics.

[30]  David A. Steinman,et al.  Path-Dependent Hemodynamics of the Stenosed Carotid Bifurcation , 2003, Annals of Biomedical Engineering.

[31]  T. Pedley The Fluid Mechanics of Large Blood Vessels: Contents , 1980 .

[32]  Jerrold E. Marsden,et al.  Transport and stirring induced by vortex formation , 2007, Journal of Fluid Mechanics.

[33]  P. Pagel,et al.  Stent Implantation Alters Coronary Artery Hemodynamics and Wall Shear Stress During Maximal Vasodilation. , 2002, Journal of applied physiology.

[34]  Timothy J. Pedley,et al.  The fluid mechanics of large blood vessels , 1980 .

[35]  Danny Bluestein,et al.  High-Shear Stress Sensitizes Platelets to Subsequent Low-Shear Conditions , 2010, Annals of Biomedical Engineering.

[36]  J. Moake,et al.  THE RESPONSE OF HUMAN PLATELETS TO SHEAR STRESS AT SHORT EXPOSURE TIMES , 1977, Transactions - American Society for Artificial Internal Organs.

[37]  Comment on "Finding finite-time invariant manifolds in two-dimensional velocity fields" [Chaos 10, 99 (2000)]. , 2001, Chaos.

[38]  Shawn C. Shadden,et al.  Lagrangian Coherent Structures , 2011 .