Dynamics of Blood Flow and Platelet Transport in Pathological Vessels

Abstract: Arterial disease, characterized by arterial occlusion (stenosis), is a leading cause of cardiovascular diseases and a major healthcare problem in the Western world. One of the main mechanisms leading to vessel occlusion is thrombus formation, which may be initiated by platelet activation. Shear rates and flow patterns (fluid dynamics factors) and concentration of coagulation factors and platelet agonists (biological factors) modulate platelet function and may lead to platelet activation and aggregation. Here, we examine the flow‐induced mechanisms leading to platelet activation in models of stenosed coronary vessels. Experimental and numerical methods were used to investigate and characterize the influence of the flow field on platelet activation. As it passes through pathological geometries characteristic of arterial stenosis, a platelet is exposed to varying levels of shear stress. The cumulative effect of the shear stress level and the duration of the platelet's exposure to it determine whether the platelet is brought beyond its activation threshold. Stress histories of individual platelets can be tracked within the flow field to locate the regions where activated platelets might be found and subsequently aggregate and/or adhere to the wall.

[1]  S. Sutera,et al.  A programmable, computer-controlled cone-plate viscometer for the application of pulsatile shear stress to platelet suspensions. , 1988, Biorheology.

[2]  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.

[3]  K Perktold,et al.  Pulsatile albumin transport in large arteries: a numerical simulation study. , 1996, Journal of biomechanical engineering.

[4]  A. Gosman,et al.  Aspects of computer simulation of liquid-fuelled combustors , 1981 .

[5]  S H Chu,et al.  Turbulence characteristics downstream of bileaflet aortic valve prostheses. , 2000, Journal of biomechanical engineering.

[6]  S. Jones A relationship between reynolds stresses and viscous dissipation: Implications to red cell damage , 2006, Annals of Biomedical Engineering.

[7]  C. Willert,et al.  Digital particle image velocimetry , 1991 .

[8]  J. O'brien,et al.  Shear-induced platelet aggregation , 1990, The Lancet.

[9]  A P Yoganathan,et al.  The sensitivity of indicators of thrombosis initiation to a bileaflet prosthesis leakage stimulus. , 2001, The Journal of heart valve disease.

[10]  H Schmid-Schönbein,et al.  Platelet and Coagulation Parameters Following Millisecond Exposure to Laminar Shear Stress , 1985, Thrombosis and Haemostasis.

[11]  Larry V. McIntire,et al.  Real-time analysis of shear-dependent thrombus formation and its blockade by inhibitors of von Willebrand factor binding to platelets. , 1993 .

[12]  H. Goldsmith,et al.  Aggregation of human platelets in an annular vortex distal to a tubular expansion. , 1979, Microvascular research.

[13]  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.

[14]  V Deplano,et al.  Experimental and numerical study of pulsatile flows through stenosis: wall shear stress analysis. , 1999, Journal of biomechanics.

[15]  S. Slack,et al.  Chapter 2 Fluid dynamic and hemorheologic considerations , 1993 .

[16]  K. Mann,et al.  Human prothrombinase complex assembly and function on isolated peripheral blood cell populations. , 1985, The Journal of biological chemistry.

[17]  M D Deshpande,et al.  Steady laminar flow through modelled vascular stenoses. , 1976, Journal of biomechanics.

[18]  Frank T. Smith,et al.  The separating flow through a severely constricted symmetric tube , 1979, Journal of Fluid Mechanics.

[19]  S. A. Ahmed,et al.  Pulsatile poststenotic flow studies with laser Doppler anemometry. , 1984, Journal of biomechanics.

[20]  P. Comfurius,et al.  Changes in membrane phospholipid distribution during platelet activation. , 1983, Biochimica et biophysica acta.

[21]  J. Moake,et al.  Platelets and shear stress. , 1996, Blood.

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

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

[24]  J. Haerem,et al.  Sudden coronary death: the occurrence of platelet aggregates in the epicardial arteries of man. , 1971, Atherosclerosis.

[25]  A. Goodall,et al.  Evaluation of Whole Blood Flow Cytometric Detection of Platelet Bound Fibrinogen on Normal Subjects and Patients with Activated Platelets , 1993, Thrombosis and Haemostasis.

[26]  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.

[27]  Todd D. Giorgio,et al.  Studies on the Mechanisms of Shear-Induced Platelet Activation , 1987 .

[28]  D. Ku,et al.  Fluid mechanics of vascular systems, diseases, and thrombosis. , 1999, Annual review of biomedical engineering.

[29]  E. Merrill,et al.  Rheology of human blood, near and at zero flow. Effects of temperature and hematocrit level. , 1963, Biophysical journal.

[30]  D. Wilcox Simulation of Transition with a Two-Equation Turbulence Model , 1994 .

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

[32]  K. Gallagher,et al.  Hemodynamic effects of controlled degrees of coronary artery stenosis in short-term and long-term studies in dogs. , 1977, The Journal of thoracic and cardiovascular surgery.

[33]  R M Hochmuth,et al.  Shear-induced aggregation and lysis of platelets. , 1976, Transactions - American Society for Artificial Internal Organs.

[34]  Sakariassen Ks,et al.  Mechanisms of thromboembolism at arterial plaques. , 1993 .

[35]  K. Gallagher,et al.  Blood Flow Reductions in Stenosed Canine Coronary Arteries: Vasospasm or Platelet Aggregation? , 1982, Circulation.

[36]  J. D. Hellums,et al.  A New Role for P-Selectin in Shear-Induced Platelet Aggregation , 2000, Circulation.

[37]  D. P. Giddens,et al.  Turbulence measurements in a constricted tube , 1980, Journal of Fluid Mechanics.

[38]  The Effect of Constriction Size on the Pulsatile Flow in a Channel , 1995 .

[39]  F N van de Vosse,et al.  Analysis of the axial flow field in stenosed carotid artery bifurcation models--LDA experiments. , 1996, Journal of biomechanics.

[40]  Richard S.C. Cobbold,et al.  Pulsatile flow through constricted tubes: an experimental investigation using photochromic tracer methods , 1989, Journal of Fluid Mechanics.

[41]  G. Tuszynski,et al.  Thrombospondin Promotes Platelet Aggregation , 1988 .

[42]  M. Deville,et al.  Pulsatile flow of non-Newtonian fluids through arterial stenoses. , 1996, Journal of biomechanics.

[43]  R Gorlin,et al.  Angiographic demonstration of a common link between unstable angina pectoris and non-Q-wave acute myocardial infarction. , 1988, The American journal of cardiology.

[44]  J Jesty,et al.  Acetylated prothrombin as a substrate in the measurement of the procoagulant activity of platelets: elimination of the feedback activation of platelets by thrombin. , 1999, Analytical biochemistry.

[45]  K. Mann,et al.  Dependence of antithrombin III and thrombin binding stoichiometries and catalytic activity on the molecular weight of affinity-purified heparin. , 1986, The Journal of biological chemistry.

[46]  C Kleinstreuer,et al.  Simulation of particle-hemodynamics in a partially occluded artery segment with implications to the initiation of microemboli and secondary stenoses. , 1998, Journal of biomechanical engineering.

[47]  H. C. Hemker,et al.  The pathways of blood coagulation , 1967 .

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

[49]  P. Perrotta,et al.  Platelet activation in a circulating flow loop: combined effects of shear stress and exposure time , 2003, Platelets.

[50]  V. Fuster,et al.  Antithrombotic therapy in acute myocardial infarction: prevention of venous, left ventricular and coronary artery thromboembolism. , 1989, The American journal of cardiology.

[51]  M. Deville,et al.  Finite element simulation of pulsatile flow through arterial stenosis. , 1992, Journal of biomechanics.

[52]  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.