Carotid Bifurcation Atherosclerosis: Quantitative Correlation of Plaque Localization with Flow Velocity Profiles and Wall Shear Stress

The distribution of nonstenosing, asymptomatic intimal plaques in 12 adult human carotid bifurcations obtained at autopsy was compared with the distribution of flow streamline patterns, flow velocity profiles, and shear stresses in corresponding scale models. The postmortem specimens were fixed while distended to restore normal in vivo length, diameter, and configura- tion. Angiograms were used to measure branch angles and diameters, and transverse histological sections were studied at five standard sampling levels. Intimal thickness was determined at 15° intervals around the circumference of the vessel sections from contour tracings of images projected onto a digitizing plate. In the models, laser-Doppler anemometry was used to determine flow velocity profiles and shear stresses at levels corresponding to the standard specimen sampling sites under conditions of steady flow at Reynolds numbers of 400, 800, and 1200, and flow patterns were visualized by hydrogen bubble and dye-washout techniques. Intimal thickening was greatest and consistently eccentric in the carotid sinus. With the center of the flow divider as the 0° index point, mid-sinus sections showed minimum intimal thickness (0.05 ± 0.02 mm) within 15° of the index point, while maximum thickness (0.9 ± 0.1 mm) occurred at 161 ± 16°, i.e., on the outer wall opposite the flow divider. Where the intima was thinnest, along the inner wall, flow streamlines in the model remain axially aligned and unidirectional, with velocity maxima shifted toward the flow divider apex. Wall shear stress along the inner wall ranged from 31 to 600 dynes/cm2 depending on the Reynolds number. Where the intima was thickest, along the outer wall opposite the flow divider apex, the pattern of flow was complex and included a region of separation and reversal of axial flow as well as the development of counter-rotating helical trajectories. Wall shear stress along the outer wall ranged from 0 to —6 dynes/cm2. Intimal thickening at the common carotid and distal internal carotid levels of section was minimal and was distributed uniformly about the circumference. We conclude that in the human carotid bifurcation, regions of moderate to high shear stress, where flow remains unidirectional and axially aligned, are relatively spared of intimal thickening. Intimal thickening and atherosclerosis develop largely in regions of relatively low wall shear stress, flow separation, and departure from axially aligned, unidirectional flow. Similar quantitative evaluations of other atherosclerosis-prone locations and corresponding flow profile studies in geometrically accurate models may reveal which of these hemodynamic conditions are most consistently associated with the development of intimal disease.

[1]  R. E. Peterson,et al.  Development and distribution of gross atherosclerotic lesions at cervical carotid bifurcation , 1960, Neurology.

[2]  G. Tindall,et al.  Studies on carotid artery flow and pressure. Observations in 18 patients during graded occlusion of proximal carotid artery. , 1962, Journal of neurosurgery.

[3]  J. Krog,et al.  Electromagnetic studies on the blood flow through the carotid system in man , 1962, Neurology.

[4]  J. Meyer,et al.  Arteriographic study of sites, incidence, and treatment of arteriosclerotic cerebrovascular lesions , 1962, Neurology.

[5]  S. Glagov,et al.  CONTROLLED PRESSURE FIXATION APPARATUS FOR HEARTS. , 1963, Archives of pathology.

[6]  H SCHARFSTEIN,et al.  Changes of Boundary Layer Flow in Model Systems: Implications For Initiation Of Endothelial Injury , 1963, Circulation research.

[7]  General findings of the International Atherosclerosis Project. , 1968, Laboratory investigation; a journal of technical methods and pathology.

[8]  D. L. Fry Acute Vascular Endothelial Changes Associated with Increased Blood Velocity Gradients , 1968, Circulation research.

[9]  J. A. Fox,et al.  Static zones in the internal carotid artery: correlation with boundary layer separation and stasis in model flows. , 1970, The British journal of radiology.

[10]  L. Solberg,et al.  Localization and Sequence of Development of Atherosclerotic Lesions in the Carotid and Vertebral Arteries , 1971, Circulation.

[11]  R. Schroter,et al.  Atheroma and arterial wall shear - Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis , 1971, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[12]  D. Heath,et al.  The atherosclerotic human carotid sinus. , 1973, The Journal of pathology.

[13]  R. Nerem,et al.  Transport of 14 C-4-cholesterol between serum and wall in the perfused dog common carotid artery. , 1973, Circulation research.

[14]  W. Gutstein,et al.  Blood flow disturbance and endothelial cell injury in preatherosclerotic swine. , 1973, Laboratory investigation; a journal of technical methods and pathology.

[15]  W. Stehbens The role of hemodynamics in the pathogenesis of atherosclerosis. , 1975, Progress in cardiovascular diseases.

[16]  J. Cornhill,et al.  A quantitative study of the localization of atherosclerotic lesions in the rabbit aorta. , 1976, Atherosclerosis.

[17]  Harry E. Petschek,et al.  Platelet aggregate formation in a region of separated blood flow , 1977 .

[18]  M. Stemerman,et al.  Intimal healing. The pattern of reendothelialization and intimal thickening. , 1977, The American journal of pathology.

[19]  M. Reidy,et al.  Scanning electron microscopy of arteries. The morphology of aortic endothelium in haemodynamically stressed areas associated with branches. , 1977, Atherosclerosis.

[20]  M. R. Roach,et al.  Artefacts of localization of atherosclerosis in pinned aortas. , 1978, Atherosclerosis.

[21]  K. Balasubramanian An experimental investigation of steady flow at an arterial bifurcation , 1979 .

[22]  F. Gorstein,et al.  The Carotid Bifurcation Plaque: Pathologic Findings Associated with Cerebral Ischemia , 1979, Stroke.

[23]  W. Insull,et al.  Role of endothelium and hypercholesterolemia in intimal thickening and lipid accumulation. , 1979, The American journal of pathology.

[24]  R. Depalma,et al.  Effect of regenerated endothelium on collagen content in the injured artery. , 1979, Surgery, gynecology & obstetrics.

[25]  C. Zarins,et al.  Endothelial integrity at aortic ostial flow dividers. , 1980, Scanning electron microscopy.

[26]  H. Sabbah,et al.  Hemorheology of turbulence. , 1980, Biorheology.

[27]  H. Sinzinger,et al.  Quantitative investigation of sudanophilic lesions around the aortic ostia of human fetuses, newborn and children. , 1980, Blood vessels.

[28]  Seymour Glagov,et al.  Quantitation of Cells and Fibers in Histologic Sections of Arterial Walls: Advantages of Contour Tracing on a Digitizing Plate , 1981 .

[29]  C. Zarins,et al.  Local Effects of Stenoses: Increased Flow Velocity Inhibits Atherogenesis , 1981, Circulation.

[30]  A. Svindland,et al.  Localization of early atherosclerotic lesions in an arterial bifurcation in humans. , 2009, Acta pathologica et microbiologica Scandinavica. Section A, Pathology.

[31]  M D Nowak,et al.  Flow Studies in a Model Carotid Bifurcation , 1981, Arteriosclerosis.

[32]  G. Hutchins,et al.  Correlation between intimal thickness and fluid shear in human arteries. , 1981, Atherosclerosis.

[33]  S. Houle,et al.  Flow studies in a rigid model of an aorto-renal junction. A case for high shear as a cause of the localization of sudanophilic lesions in rabbits. , 1981, Atherosclerosis.

[34]  Complicating factors in evaluating coronary artery atherosclerosis. , 1981, Artery.

[35]  R. Ross George Lyman Duff Memorial Lecture. Atherosclerosis: a problem of the biology of arterial wall cells and their interactions with blood components. , 1981, Arteriosclerosis.

[36]  G. Majno,et al.  Hydrodynamic injury of the endothelium in acute aortic stenosis. , 1982, The American journal of pathology.

[37]  D. Giddens,et al.  Steady flow in a model of the human carotid bifurcation. Part II--laser-Doppler anemometer measurements. , 1982, Journal of biomechanics.

[38]  D. Giddens,et al.  Steady flow in a model of the human carotid bifurcation. Part I--flow visualization. , 1982, Journal of biomechanics.

[39]  C. Zarins,et al.  Correlation of Postmortem Angiography with Pathologic Anatomy , 1983 .

[40]  D. Ku,et al.  Pulsatile Flow in a Model Carotid Bifurcation , 1983, Arteriosclerosis.