A Mechanistic Model of Acute Platelet Accumulation in Thrombogenic Stenoses

AbstractThrombosis on an atherosclerotic lesion can cause heart attack or stroke. Thrombosis may be triggered by plaque rupture or erosion, creating a thrombogenic stenosis. To measure and model this situation, collagen-coated stenoses have been exposed to nonanticoagulated blood in a baboon ex vivo shunt. The maximum rate of platelet accumulation, measured using a gamma camera, was highest in the throat region of moderate and severe stenoses, and increased with increasing stenosis severity. A species transport model of platelet accumulation was developed, which included mechanisms of convection, shear-enhanced diffusion, near-wall platelet concentration, and a kinetic model of platelet activation and aggregation. The model accurately reproduced the average spatial pattern and time rate of platelet accumulation in the upstream and throat regions of the stenosis, where shear-enhanced diffusivity increased platelet transport in the stenosis throat. Downstream of the throat where flow is complicated by recirculation, the model computed a transport-limited region with lower than measured platelet accumulation, suggesting that fluid-phase platelet activation may significantly affect both transport and adhesion rates in the poststenotic region. This model may provide an initial quantitative estimate of the likelihood of occlusive thrombus in individual patients due to plaque erosion, artery spasm, incomplete angioplasty, or plaque rupture. © 2001 Biomedical Engineering Society. PAC01: 8717Aa, 8719Tt, 8719Xx

[1]  S. Hanson,et al.  Platelet Interactions with Dacron Vascular Grafts: A Model of Acute Thrombosis in Baboons , 1985, Arteriosclerosis.

[2]  James F. Antaki,et al.  Computational Simulation of Platelet Deposition and Activation: I. Model Development and Properties , 1999, Annals of Biomedical Engineering.

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

[4]  Diran Basmadjian,et al.  The effect of flow and mass transport in thrombogenesis , 2006, Annals of Biomedical Engineering.

[5]  C. Warlow,et al.  MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis , 1991, The Lancet.

[6]  D. Waters,et al.  Platelet aggregation, coronary artery disease progression and future coronary events. , 1994, The American journal of cardiology.

[7]  A. Beaudoin,et al.  Analysis of shear stress and hemodynamic factors in a model of coronary artery stenosis and thrombosis. , 1993, The American journal of physiology.

[8]  J D Hellums,et al.  Aggregation and disaggregation kinetics of human blood platelets: Part II. Shear-induced platelet aggregation. , 1993, Biophysical journal.

[9]  I. Ringqvist,et al.  Effect of coronary bypass surgery on survival patterns in subsets of patients with left main coronary artery disease. Report of the Collaborative Study in Coronary Artery Surgery (CASS). , 1981, The American journal of cardiology.

[10]  Danny Bluestein,et al.  Vortex Shedding in Steady Flow Through a Model of an Arterial Stenosis and Its Relevance to Mural Platelet Deposition , 1999, Annals of Biomedical Engineering.

[11]  J. Hubbell,et al.  Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood. , 1990, The Journal of laboratory and clinical medicine.

[12]  H. Weiss,et al.  The effect of shear rate on platelet interaction with subendothelium exposed to citrated human blood. , 1980, Microvascular research.

[13]  M J Davies,et al.  A macro and micro view of coronary vascular insult in ischemic heart disease. , 1990, Circulation.

[14]  A. Davies,et al.  Endarterectomy for asymptomatic carotid artery stenosis , 1995, BMJ.

[15]  P Constantinides,et al.  Cause of thrombosis in human atherosclerotic arteries. , 1990, The American journal of cardiology.

[16]  H. Baumgartner,et al.  Measurements of platelet interaction with components of the vessel wall in flowing blood. , 1989, Methods in enzymology.

[17]  V. Turitto,et al.  Platelet deposition on subendothelium exposed to flowing blood: mathematical analysis of physical parameters. , 1975, Transactions - American Society for Artificial Internal Organs.

[18]  James F. Antaki,et al.  Computational Simulation of Platelet Deposition and Activation: II. Results for Poiseuille Flow over Collagen , 1999, Annals of Biomedical Engineering.

[19]  J. Schapiro,et al.  Platelet hyperreactivity and prognosis in survivors of myocardial infarction. , 1990, The New England journal of medicine.

[20]  M J Davies,et al.  Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. , 1984, The New England journal of medicine.

[21]  R M Heethaar,et al.  Blood platelets are concentrated near the wall and red blood cells, in the center in flowing blood. , 1988, Arteriosclerosis.

[22]  J. Badimón,et al.  Mechanisms of arterial thrombosis in nonparallel streamlines: platelet thrombi grow on the apex of stenotic severely injured vessel wall. Experimental study in the pig model. , 1989, The Journal of clinical investigation.

[23]  S. Hanson,et al.  Reduction in stent and vascular graft thrombosis and enhancement of thrombolysis by recombinant Lys-plasminogen in nonhuman primates. , 1997, Circulation.

[24]  J. M. Siegel,et al.  A scaling law for wall shear rate through an arterial stenosis. , 1994, Journal of biomechanical engineering.

[25]  A. Svindland,et al.  Pathogenesis of carotid thrombosis. , 1989, Stroke.

[26]  G. T. Jones.  Blood platelet count and function are related to total and cardiovascular death in apparently healthy men , 1992 .

[27]  D. Sackett,et al.  Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. , 1991, The New England journal of medicine.

[28]  E. Eckstein,et al.  Model of platelet transport in flowing blood with drift and diffusion terms. , 1991, Biophysical journal.

[29]  L V McIntire,et al.  Mathematical analysis of mural thrombogenesis. Concentration profiles of platelet-activating agents and effects of viscous shear flow. , 1989, Biophysical journal.

[30]  S. Sukavaneshvar,et al.  Enhancement of Stent-Induced Thromboembolism by Residual Stenoses: Contribution of Hemodynamics , 2000, Annals of Biomedical Engineering.

[31]  R N Vaishnav,et al.  Determination of the local erosion stress of the canine endothelium using a jet impingement method. , 1983, Journal of biomechanical engineering.

[32]  J. Folts,et al.  Platelet Aggregation in Partially Obstructed Vessels and its Elimination with Aspirin , 1976, Circulation.

[33]  S. Hanson,et al.  The relation of platelet density to platelet age: survival of low- and high-density 111indium-labeled platelets in baboons. , 1986, Blood.

[34]  Stanley E. Rittgers,et al.  Particle Motion Within In Vitro Models of Stenosed Internal Carotid and Left Anterior Descending Coronary Arteries , 1998, Annals of Biomedical Engineering.

[35]  P. Elwood,et al.  Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study. , 1991, Circulation.

[36]  G. Sicard.  MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70–99%) or mild (0–29%) carotid stenosis: European Carotid Surgery Trialist' Collaborative Group. Lancet 1991;337:1235-43 , 1992 .

[37]  R. Virmani,et al.  Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction , 1998, Heart.