Joint US-Sweden workshop: the role of university research in the future development of the biomedical industry.
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Congresses as Topic↗
Biomedical subjects
R M Nerem
Publications and source records attributed to R M Nerem.
Epicardial coronary blood flow including the presence of stenoses and aorto-coronary bypasses--II: Experimental comparison and parametric investigations.
This article is the second in a series which presents a computer model of the left coronary arteries. The first article discussed the geometry, the governing equations, and the numerical method employed. This paper details an acute canine experiment used to validate the approach as well as the systematic investigation of several important parameters governing the left coronary circulation. These parameters include peripheral resistance, wall properties, and altered geometric properties through various stenosis/bypass configurations. With appropriate selection of parameters, the model reproduces an in vivo waveform very closely. The model also predicts many clinical phenomena, such as the "critical" value of stenosis, the dramatic reduction in flow through a stenosis when bypassed, and the restorative effect of the bypass upon flow to the distal bed. The model also is used to show that the autonomic state of the animal profoundly affects the influence of various factors, e.g., the critical value of a stenosis is much higher under resting conditions than under hyperemic conditions.
Algorithms↗
The application of a homogeneous half-space model in the analysis of endothelial cell micropipette measurements.
Experimental studies have shown that endothelial cells which have been exposed to shear stress maintain a flattened and elongated shape after detachment. Their mechanical properties, which are studied using the micropipette experiments, are influenced by the level as well as the duration of the shear stress. In the present paper, we analyze these mechanical properties with the aid of two mathematical models suggested by the micropipette technique and by the geometry peculiar to these cells in their detached post-exposure state. The two models differ in their treatment of the contact zone between the cell and the micropipette. The main results are expressions for an effective Young's modulus for the cells, which are used in conjunction with the micropipette data to determine an effective Young's modulus for bovine endothelial cells, and to discuss the dependence of this modulus upon exposure to shear stress.
Animals↗
An application of the micropipette technique to the measurement of the mechanical properties of cultured bovine aortic endothelial cells.
The mechanical properties of endothelial cells were measured using the micropipette technique. The cells employed were collected from bovine aortic endothelium and cultured in our laboratory. Endothelial cells from confluent monolayers under no-flow conditions were detached from their substrate by trypsin or by a mechanical method and suspended in modified Dulbecco medium (MDM). In the micropipette technique, a part of the cell is aspirated into the tip of the micropipette under a microscope, and the deformation measured from a photograph. In this study, the data obtained were analyzed using a model where the cytoskeletal elements, which are considered to be the primary stress bearing components, are assumed to reside in a submembranous, cortical layer. Detached cells were found to have almost homogeneous mechanical properties based on measurements from different regions of the surface of a single cell. However, a hysteresis loop was observed in the relation between pressure and cell deformation during the loading and unloading processes. The calculated elastic shear moduli obtained for the trypsin-detached cells were as much as 10-20 times larger than those of a red blood cell. Mechanically-detached cells had moduli approximately twice that of the trypsin detached cells. Passage time, i.e., cell culture age, had no influence on the mechanical properties of the trypsin-detached cells, but did have an effect on the mechanically-detached cells, with both the younger and older cells being somewhat stiffer.
Actins↗
Influence of a laminar steady-state fluid-imposed wall shear stress on the binding, internalization, and degradation of low-density lipoproteins by cultured arterial endothelium.
Fluid mechanical steady-state laminar wall shear stresses of 30 dyne/cm2 (high stress) and less than 1 dyne/cm2 (low stress) have been applied for varying times to confluent cultures of bovine aortic endothelial cells (BAECs) by means of two parallel plate channel flow chambers in series. BAEC cultures not exposed to shear or flow (no stress) were also studied. A shear stress of 30 dyne/cm2 resulted in cellular elongation and alignment, changes that were largely complete by 24 hr. In experiments in which BAECs were incubated with 125I-labeled low-density lipoprotein for 2 or 24 hr in the presence of shear stress levels, 125I-LDL internalization at 24 hr was increased (p less than .05) in response to high-stress conditions. This increased uptake of 125I-LDL was observed in BAECs prealigned for 24 hr under high stress and in BAECs undergoing alignment in the presence of circulating 125I-LDL. BAECs were also exposed to shear stress for 24 hr in the presence of a lipoprotein-deficient circulating medium to maximize LDL receptor expression. Receptor-mediated 125I-LDL internalization and degradation measured immediately after shear stress were both significantly enhanced (p less than .01) in BAECs exposed to high stress. Furthermore, 125I-LDL binding studies at 4 degrees C revealed a significant increase (p less than .01) in specific 125I-LDL binding to BAECs exposed to high stress relative to those exposed to low or no stress. Nonspecific 125I-LDL endocytosis was not influenced by shear stress levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
An experimental study of coronary artery fluid mechanics.
Preserved baboon and canine hearts were perfused using an in-vitro pulsatile flow system. Flow rate and pulsation frequency were controlled, and velocity profile measurements were made at several sites on the left epicardial coronary arteries of each heart. Velocity profiles were measured using a multi-channel, pulsed ultrasonic Doppler velocimeter, and the data were processed with a laboratory microcomputer system. Flow in the left main coronary artery appeared to be similar to descriptions of developing curved tube flow, but an unexplained oscillation of the velocity profiles was observed in this artery. Near the bifurcation of the main coronary artery into the anterior descending and the circumflex, the pattern of velocity profile skewing appeared to be determined by the angle through which the daughter vessels turned from the main and the overall curvature of the "plane" of bifurcation. Several diameters downstream from the bifurcation the flow appeared to be quasi-steady.
Animals↗
The elongation and orientation of cultured endothelial cells in response to shear stress.
Vascular endothelial cells appear to be aligned with the flow in the immediate vicinity of the arterial wall and have a shape which is more ellipsoidal in regions of high shear and more polygonal in regions of low shear stress. In order to study quantitatively the nature of this response, bovine aortic endothelial cells grown on Thermanox plastic coverslips were exposed to shear stress levels of 10, 30, and 85 dynes/cm2 for periods up to 24 hr using a parallel plate flow chamber. A computer-based analysis system was used to quantify the degree of cell elongation with respect to the change in cell angle of orientation and with time. The results show that (i) endothelial cells orient with the flow direction under the influence of shear stress, (ii) the time required for cell alignment with flow direction is somewhat longer than that required for cell elongation, (iii) there is a strong correlation between the degree of alignment and endothelial cell shape, and (iv) endothelial cells become more elongated when exposed to higher shear stresses.
Animals↗
Epicardial coronary blood flow including the presence of stenoses and aorto-coronary bypasses--I: Model and numerical method.
A computer model and numerical method for calculating left epicardial coronary blood flow has been developed. This model employs a finite-branching geometry of the coronary vasculature and the one-dimensional, unsteady equations for flow with friction. The epicardial coronary geometry includes the left main and its bifurcation, the left anterior descending and left circumflex coronary arteries, and a selected number of small branches. Each of the latter terminate in an impedance, whose resistive component is related to intramyocardial compression through a linear dependence on left ventricular pressure. The elastic properties of the epicardial arteries are taken to be non-linear and are prescribed by specifying the local small-disturbance wave speed. The model allows for the incorporation of multiple stenoses as well as aorto-coronary bypasses. Calculations using this model predict pressure and flow waveform development and allow for the systematic investigation of the dependence of coronary flow on various parameters, e.g., peripheral resistance, wall properties, and branching pattern, as well as the presence of stenoses and bypass grafts. Reasonable comparison between calculations and earlier experiments in horses has been obtained.
Animals↗
Turbulence in pulsatile flows.
Turbulence during pulsatile flow has been suggested as a possible mechanism to enhance the transport of gases during high-frequency ventilation. Experimental studies on oscillatory flow in straight, circular tubes have identified three types of flow: (a) laminar; (b) conditionally turbulent, in which high-frequency disturbances occur during the decelerating phase of the flow cycle but relaminarize by the beginning of the subsequent accelerating phase; and (c) fully turbulent flow, in which disturbances occur throughout the flow cycle. Fully turbulent flow has been observed only when a mean flow is present, and only laminar or conditionally turbulent flow has been observed for purely oscillatory flow. A critical Reynolds number based on the Stokes layer can be defined, and transition Reynolds numbers between 400 and 550 have been experimentally determined for purely oscillatory flow in a circular tube, although lower values are expected for physiological flows. There are some indications that the structure of oscillating turbulent flow is similar to steady turbulent flow, and preliminary work in our laboratory shows that the spectral content of flows during high-frequency ventilation is similar to that in steady turbulent flow.
Animals↗
On the propagation of a wave front in viscoelastic arteries.
In formulating a mathematical model of the arterial system, the one-dimensional flow approximation yields realistic pressure and flow pulses in the proximal as well as in the distal regions of a simulated arterial conduit, provided that the viscoelastic damping induced by the vessel wall is properly taken into account. Models which are based on a purely elastic formulation of the arterial wall properties are known to produce shocklike transitions in the propagating pulses which are not observed in man under physiological conditions. The viscoelastic damping characteristics are such that they are expected to reduce the tendency of shock formation in the model. In order to analyze this phenomenon, the propagation of first and second-order pressure waves is calculated with the aid of a wave front expansion, and criteria for the formation of shocks are derived. The application of the results to the human arterial system show that shock waves are not to be expected under normal conditions, while in case of a pathologically increased pressure rise at the root of the aorta, shocklike transitions may develop in the periphery. In particular, it is shown that second-order waves never lead to shock formation in finite time for the class of initial conditions and mechanical wave guides which are of interest in the mammalian circulation.
Arteries↗
Atherogenesis: hemodynamics, vascular geometry, and the endothelium.
The evidence for a hemodynamic involvement and possible mechanisms by which hemodynamic-related events could influence the arterial wall, and in particular the vascular endothelium, are reviewed and used to speculate on the role of fluid mechanics in atherogenesis and specifically in lesion localization. The evidence presented suggests that it is vascular geometry, and the way it influences the local detailed flow properties, which is the primary determinant of a hemodynamic effect on the arterial wall and in the initiation of atherosclerosis.
Animals↗
Fluid dynamics as a factor in the localization of atherogenesis.
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Animals↗
Model study of flow in curved and planar arterial bifurcations.
Velocity profile measurements have been made for steady and pulsatile flow within rigid tube models of a curved and a planar arterial bifurcation with the intent of providing some insight into the fluid mechanical forces existing at such branches. An example in the cardiovascular system of a curved bifurcation is the branching of the left common coronary artery into the left circumflex and left anterior descending coronary arteries where the vessels curve over the base of the heart and an example of a planar bifurcation is the branching of the abdominal aorta into the left and right iliac arteries. Point velocity measurements were carried out using a constant temperature hot-film anemometer system.
Animals↗
Vascular endothelial morphology as an indicator of the pattern of blood flow.
A quantitative study of the en face size and shape of endothelial cells from aortic intercostal ostia has been carried out in rabbits. Photomicrographs were taken from vascular casts of the rabbit aorta and the endothelial cell outlines were analyzed quantitatively using a digitizer and digital computer. The morphology of the endothelial cells was described using 8 calculated parameters (area, perimeter, length, width, angle of orientation, width: length ratio, axis-intersection ratio and shape index). Marked changes in cell morphology were found in the regions proximal and distal to ostia as well as around flow dividers. Cells on the aorta are aligned with the flow direction, and the endothelial cells within the ostia have an angle of orientation of approximately 45 deg to the axis of the vessel. The results obtained to date suggest that endothelial cell morphology and orientation around a branch vessel may be a natural marker or indicator of the detailed features of blood flow.
Animals↗
Social environment as a factor in diet-induced atherosclerosis.
Rabbits on a 2 percent cholesterol diet were individually petted, held, talked to, and played with on a regular basis. Measurements of aortic affinity for a Sudan stain, serum cholesterol levels, heart rate, and blood pressure were made at the end of the experimental period. Compared to control groups, which were given the same diet and normal laboratory animal care, the experimental groups showed more than a 60 percent reduction in the percentage of aortic surface area exhibiting sudanophilic lesions, even though serum cholesterol levels, heart rate, and blood pressure were comparable.
Animals↗
Quantitative study of the localization of sudanophilic coeliac lesions in the White Carneau pigeon.
Polar coordinate mapping was used to determine the rate of progression of spontaneous sudanophilic coeliac lesions on the aortic wall in White Carneau pigeons. Three age groups of 5 pigeons were studied (approximately 1, 4 approximately 4 and approximately 6.5 years). Serum cholesterol was found to decrease with age (r = 0.69, P less than 0.01). Lesion area was found to increase with both age (r = 0.86, P less than 0.01) and the age--serum cholesterol product (r = 0.92, P less than 0.01). Lesions developed initially in the proximal sector (270 degrees leads to 90 degrees) with two relative maxima (approximately 20 degrees and approximately 320 degrees). Lesions then grow proximally and radially. The immediately proximal inflow region (340 degrees leads to 360 degrees) was spared in all 3 age groups. Little sudanophilic material was observed on the distal flow divider (90 degrees leads to 270 degrees) even in the oldest birds. The mode of spontaneous coeliac sudanophilic lesion development in the White Carneau pigeon is in sharp contrast to that observed both in spontaneous lesions in human infants and in experimental lesions in the hypercholesterolemic rabbit where lesion development is in the distal sector (90 degrees leads to 270 degrees).
Animals↗
Quantitative study of the rabbit aortic endothelium using vascular casts.
A quantitative study of the en face size and shape of rabbit endothelial cells from the ventral mid-thoracic and ventral infrarenal abdominal aorta has been carried out in 6 rabbits. Photomicrographs were taken from vascular casts of the rabbit aorta and the endothelial cell outlines were analyzed quantitatively using a digitizer and digital computer. The morphology of the endothelial cells was described using 8 calculated parameters (area, perimeter, length, width, angle of orientation, width:length ratio, axis intersection ratio and shape index). The endothelial cells in both locations had the same surface area (P greater than 0.30); however, the cells in the abdominal aorta were longer (P less than 0.01) and narrower (P less than 0.01) than those in the thoracic aorta. This fact is reflected by the smaller value for the shape index and width : length ratio in the abdominal aorta (P less than 0.01). Cells in both the thoracic and abdominal aorta were aligned with the flow direction.
Animals↗
Hemodynamics and atherogenesis.
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Animals↗