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Biomedical subjects

H L Goldsmith

Publications and source records attributed to H L Goldsmith.

At least 37 records · Page 2Linked to original sources

Flow patterns at the major T-junctions of the dog descending aorta.

Using a novel technique developed in our own laboratory, an isolated transparent arterial segment containing the whole descending aorta and its four major branches was prepared from a dog. The flow patterns at each aortic T-junction were studied in detail under the conditions of steady flow by means of flow visualization and cinemicrographic techniques. It was found that a standing recirculation zone consisting of a pair of thin-layered spiral secondary flows located symmetrically about the common median plane of the aorta and side branches was formed at each T-junction over a wide range of flow conditions including the time-averaged estimated mean values of physiological flow rates and flow rate ratios. The results support the recent in vivo findings by other investigators that flow reversal occurs at some junctions of the dog abdominal aorta during each cardiac cycle. The flow patterns at the aortic T-junctions were very much similar to those previously observed in various glass model T-junctions. However, due to the particular anatomical structure of the vessel wall at each branching site (the curvature of the wall was very sharp at the flow divider, but gently rounded at the bend opposite to it) no recirculation zone was formed in the side branches. At a given flow rate ratio, the measured critical Reynolds numbers for the formation of spiral secondary flows and fully developed disturbed flows were much higher in aortic T-junctions than those in glass model T-junctions having equivalent branching angles and diameter ratios. These results indicate that, in the circulation, conditions at arterial T-junctions appear to be optimal for minimizing the formation of disturbed flows.

Animals↗

Adenosine diphosphate-induced aggregation of human platelets in flow through tubes. I. Measurement of concentration and size of single platelets and aggregates.

A double infusion flow system and particle sizing technique were developed to study the effect of time and shear rate on adenosine diphosphate-induced platelet aggregation in Poiseuille flow. Citrated platelet-rich plasma, PRP, and 2 microM ADP were simultaneously infused into a 40-microliters cylindrical mixing chamber at a fixed flow ratio, PRP/ADP = 9:1. After rapid mixing by a rotating magnetic stirbar, the platelet suspension flowed through 1.19 or 0.76 mm i.d. polyethylene tubing for mean transit times, t, from 0.1 to 86 s, over a range of mean tube shear rate, G, from 41.9 to 1,000 s-1. Known volumes of suspension were collected into 0.5% buffered glutaraldehyde, and all particles in the volume range 1-10(5) microns 3 were counted and sized using a model ZM particle counter (Coulter Electronics Inc., Hialeah, FL) and a logarithmic amplifier. The decrease in the single platelet concentration served as an overall index of aggregation. The decrease in the total particle concentration was used to calculate the collision capture efficiency during the early stages of aggregation, and aggregate growth was followed by changes in the volume fraction of particles of successively increasing size. Preliminary results demonstrate that both collision efficiency and particle volume fraction reveal important aspects of the aggregation process not indicated by changes in the single platelet concentration alone.

Adenosine Diphosphate↗

Adenosine diphosphate-induced aggregation of human platelets in flow through tubes. II. Effect of shear rate, donor sex, and ADP concentration.

The effect of shear rate on the adenosine diphosphate-induced aggregation of human platelets in Poiseuille flow was studied using the method described in part I (Bell, D.N., S. Spain, and H.L. Goldsmith. 1989. Biophys. J. 56:817-828). The rate and extent of aggregation in citrated platelet-rich plasma were measured over a range of mean transit time from 0.2 to 8.6 s and mean tube shear rate, G, from 41.9 to 1,920 s-1. At 0.2 microM ADP, changes in the single platelet concentration with time suggest that more than one type of platelet-platelet bond mediates platelet aggregation at physiological shear rates. At low G, a high initial rate of aggregation reflects the formation of a weak bond of high affinity, the strength of which diminishes with time. Here, the fraction of collisions yielding stable doublets, the collision efficiency, reached a maximum of 26%. The collision efficiency decreased with increasing G and was accompanied by a progressive delay in the onset of aggregation. However, the gradual expression of a more shear rate-resistant bond at high shear rates and long mean transit times produced a subsequent increase in collision efficiency and a corresponding increase in the rate of aggregation. Although the collision efficiencies here were less than 1%, the high collision frequencies were able to sustain a high rate of aggregation. At 0.2 microM ADP, aggregate size generally decreased with increasing G. At 1.0 microM ADP, aggregate size was still limited at high shear rates even though the rate of single platelet aggregation was much higher than at 0.2 microM ADP. Platelet aggregation was greater for female than for male donors, an effect related to differences in the hematocrit of donors before preparing platelet-rich plasma.

Adenosine Diphosphate↗

Robin Fåhraeus: evolution of his concepts in cardiovascular physiology.

We give an account of the work of Robin Fåhraeus over the years 1917-1938, his contribution to our understanding of blood rheology, and its relevance to circulatory physiology. Fåhraeus published few original papers on this subject, yet he clearly understood the phenomena occurring in the tube flow of mammalian blood. 1) The concentration of cells in a tube less than 0.3 mm in diameter differs from that in the larger feed tube or reservoir, the Fåhraeus effect. This is due to a difference in the mean velocity of cells and plasma in the smaller vessel associated with a nonuniform distribution of the cells. 2) In tubes less than 0.3 mm in diameter, the resistance to blood flow decreases with decreasing tube diameter, the Fåhraeus-Lindqvist effect. We define and generalize the two effects and describe how red cell aggregation at low shear rates affects cell vessel concentration and resistance to flow. The fluid mechanical principles underlying blood cell lateral migration in tube flow and its application to Fåhraeus' work are discussed. Experimental data on the Fåhraeus and Fåhraeus-Lindqvist effects are given for red cells, white cells, and platelets. Finally, the extension of the classical Fåhraeus effect to microcirculatory beds, the Fåhraeus Network effect, is described. One of the explanations for the observed, very low average capillary hematocrits is that the low values are due to a combination of the repeated phase separation of red cells and plasma at capillary bifurcations (network effect) and the single-vessel Fåhraeus effect.

Cardiovascular Physiological Phenomena↗

Interaction forces between red cells agglutinated by antibody. III. Micromanipulation.

In the flow studies described in two previous papers (Tha, S. P., and H. L. Goldsmith, 1986, Biophys. J. 50:1109-1116; Tha, S. P., J. Shuster, and H. L. Goldsmith, 1986, Biophys. J. 50:1117-1126), hydrodynamic forces of the order of 10(-11) N (mu dyn) were applied to measure the force of separation of doublets of hardened, sphered human red blood cells cross-linked by anti-B antibody. The same cell preparation and hyperimmune antiserum has here been used to carry out experiments with micropipet aspiration techniques. One cell of a doublet was aspirated onto a holding pipet, and a second aspiration pipet was brought into proximity of the other cell so that the two pipets and the doublet were colinear. Suction was then raised until the two cells separated. Some doublets were assembled by aspiration of a singlet, bringing a second singlet into apposition with the first, and releasing it from the pipet which was then withdrawn. Cells could be repeatedly assembled and separated. At 3.56% vol/vol antiserum, the mean normal force of separation was 0.45 +/- 0.11 nN in phosphate-buffered saline suspensions containing 2.5 x 10(4) cells/microliter; at 1.22% vol/vol antiserum, the value was 0.22 +/- 0.11 nN. The above values of the force were approximately 2.5 x greater than those from the flow studies. The data could be fitted to a Poisson distribution with 0.05 nN as the force needed to break a single cross-bridge (c.f. 0.024 nN from the previous hydrodynamic data). The forces of separation of randomly assembled doublets were lower than those of preexisting doublets. Repeated assembly and separation of doublets showed that the cell surfaces are nonuniform in adhesion strength both over the local scale less than 0.25 micron2 and the cell population.

Antibodies↗

Interaction forces between red cells agglutinated by antibody. I. Theoretical.

A general method of calculating forces, torques, and translational and rotational velocities of rigid, neutrally buoyant spheres suspended in viscous liquids undergoing a uniform shear flow has been given by Arp and Mason (1977). The method is based on the matrix formulation of hydrodynamic resistances in creeping flow by Brenner and O'Neill (1972). We describe the solution of the Brenner-O'Neill force-torque vector equation in terms of the particle and external flow field coordinates and derive expressions for the normal force acting along, and the shear force acting perpendicular to, the axis of the doublet of spheres, the latter explicitly given for the first time. The equations consist of a term comprising force and torque coefficients obtained from the matrices of the hydrodynamic resistances (functions of the distance h between sphere surfaces which have been computed), and terms comprising the orientation of the doublet axis relative to the coordinates of the external flow field and the shear stress (which can be experimentally determined). We have applied the theory to a system of doublets of sphered, hardened human red cells of group A or B antigenic type cross-linked by the corresponding antibody at a fixed interparticle distance. Working from studies of the breakup of doublets of red cells in an accelerating Poiseuille flow, given in the succeeding paper, we are able to compute the hydrodynamic force required to separate the two spheres. Previous work has shown that the theory can be applied to doublets in a variable shear, Poiseuille flow, provided the ratio of particle to tube diameter is small. In calculating the force-torque coefficients it was assumed that the cells are crosslinked by antibody with h = 20 nm.

ABO Blood-Group System↗

Interaction forces between red cells agglutinated by antibody. II. Measurement of hydrodynamic force of breakup.

The expressions derived in the previous paper for the respective normal, F3, and shear forces, Fshear, acting along and perpendicular to the axis of a doublet of rigid spheres, were used to determine the hydrodynamic forces required to separate two red cell spheres of antigenic type B crosslinked by the corresponding antibody. Cells were sphered and swollen in isotonic buffered glycerol containing 8 X 10(-5) M sodium dodecyl sulfate, fixed in 0.085% glutaraldehyde, and suspended in aqueous glycerol (viscosity: 15-34 mPa s), containing 0.15 M NaCl and anti-B antibody from human hyperimmune antiserum at concentrations from 0.73 to 3.56 vol%. After incubating and mixing for 12 h, doublets were observed through a microscope flowing in a 178-micron tube by gravity feed between two reservoirs. Using a traveling microtube apparatus, the doublets were tracked in a constantly accelerating flow and the translational and rotational motions were recorded on videotape until breakup occurred. From a frame by frame replay of the tape, the radial position, velocity and orientation of the doublet were obtained and the normal and shear forces of separation at breakup computed. Both forces increased significantly with increasing antiserum concentration, the mean values of F3 increasing from 0.060 to 0.197 nN, and Fshear from 0.023 to 0.072 nN. There was no significant effect of glycerol viscosity on the forces of separation. It was not possible to determine whether the shear or normal force was responsible for doublet separation. Measurements of the mean dimensionless period of rotation, TG, of doublets in suspensions containing 0.73 and 2.40% antiserum undergoing steady flow were also made to test whether the spheres were rigidly linked or capable of some independent rotation. A fairly narrow distribution in TG about the value 15.64, predicted for rigidly-linked doublets, was obtained at both antiserum concentrations.

Antibodies↗

Disturbances of flow through transparent dog aortic arch.

The present study was carried out to determine the hydrodynamic structure of flow in an aortic arch and to correlate the findings with the possible involvement of fluid dynamics in atherogenesis and thrombogenesis. Each aorta was made transparent under a transmural pressure of 100 mmHg to maintain its in vivo configuration. Methyl salicylate with a kinematic viscosity of 2.6 cSt was substituted for blood and polystyrene microspheres, 0.08-0.30 mm in diameter, were used to trace the streamlines of the flow. Flow disturbances observed in the aortic arch have characteristics similar to those of secondary flow, which is called the horseshoe vortex, produced at Y- and T-junctions. The particles captured by the secondary flow near the flow divider, for instance, moved in a direction opposite or perpendicular to the mean flow. The vortex produced a typical stagnation region at the wall of the aorta just proximal to the branching site of the brachiocephalic and the left subclavian arteries. When the rate of flow to a daughter branch decreased, separation of the flow occurred at the proximal outer wall of the branch artery. Comparison between the present results and the topographical patterns of atherosclerosis reported in the literature suggests that it is in such low-shear regions that lipid deposition tends to occur most frequently.

Animals↗

Particle flow behavior in models of branching vessels. II. Effects of branching angle and diameter ratio on flow patterns.

To further elucidate the role of fluid mechanical factors in the localization of atherogenesis and thrombogenesis, we have studied the 3-dimensional flow patterns in square T-junctions with branching angles theta from 30 degrees to 150 degrees and diameter ratios d/D (side: main tube) from 1.05/3.0 to 1.0. Cine films of the motions of tracer microspheres in dilute suspensions were taken at inflow Reynolds numbers from 15 to 400 and flow ratios (main: side tube) from 0.1 to 4.0. Flow patterns with suspension entering through the main tube were similar to those previously described in uniform 3 mm diameter T-junctions: paired vortices (spiral secondary flows) symmetrical about the common median plane formed at the entrances of the main and side daughter tubes. Particles circulated through the main vortex, some crossing above and below the mainstream into and through the side vortex. At the geometrical flow ratio, the main vortex became smaller and smaller as the branching angle (theta less than 90 degrees) and diameter ratio decreased, and was confined to a thin side tube was a minimum. In obtuse angle T-junctions the stagnation point shifted from the flow divider into the side tube, enhancing the flow disturbance there. The velocity distributions in main and side tubes were skewed towards the inner walls close to the flow divider. When flow entered through the side tube, a pair of recirculation zones formed in the main tube at the inner wall of the bend with a sharper angle.

Animals↗

Margination of leukocytes in blood flow through small tubes.

Leukocyte margination in the vessels of the microcirculation has been attributed to a flow-dependent interaction with red cells. To determine the extent of this effect, experiments with human blood were done in 100- to 180-micron tubes to detect changes in cell distribution as a function of hematocrit and flow rate. Using a flow visualization technique, the leukocyte concentration distribution was determined in 45% ghost cell suspensions. Migration of cells toward the wall was observed at centerline velocities greater than 1 mm sec-1 and increased with increasing flow rate. The effect was probably due to a more rapid inward migration of ghosts than leukocytes because of fluid inertia and cell density differences. Experiments were therefore carried out in whole blood at hematocrits from 20 to 60%, measuring the number concentration of leukocytes and erythrocytes within the tube, nt, and comparing it to that in the infusing reservoir, no, (Fahraeus effect). At mean tube shear rates G less than 100 sec-1, nt/no less than 1 for both leukocytes and erythrocytes showing net migration of cells away from the wall, although at nearly all hematocrits there was an enrichment of leukocytes relative to erythrocytes in the tubes. At G less than 50 sec-1, nt/no remained less than 1 for erythrocytes but increased to greater than 1 for leukocytes showing migration toward the wall, the increase being greatest at 20% hematocrit in the 100-micron tubes. The nature of the effect was revealed by cine films which showed that, as the flow rate decreased, erythrocytes formed rouleaux which migrated inward creating a core and displacing leukocytes to the periphery. In control experiments using washed blood cells in phosphate buffer-albumin, nt/no less than 1 for both leukocytes and erythrocytes at all G and hematocrits, and leukocytes were now distributed. Cine films of washed blood confirmed that, in the absence of rouleaux, no significant inward migration of erythrocytes occurred.

Cell Movement↗

Platelet aggregation in poiseuille flow: I. A double infusion technique.

This paper describes the design of a double infusion microtube and its use to directly observe the aggregation of platelets undergoing Poiseuille flow immediately after the introduction of 1 microM ADP. Citrated human platelet-rich plasma flowed between two reservoirs through a 100-microns-diameter flow tube at the entrance of which ADP was simultaneously infused through the tip of a concentrically located micropipet . With the aid of microcinematography, the time course of platelet aggregation was followed by measuring the number distribution of single cells and aggregates across the median plane of the tube at various distances downstream of the micropipet . Preliminary studies covering a range of mean tube shear rates from 2 to 30 sec-1 showed that, for a given donor, the fraction of platelets in aggregates, both in control runs (infusion of Tyrodes ) and in experimental runs (infusion of ADP) was reproducible to within +/- 1%. Except at the lowest shear rate, the extent of aggregation increased with increasing distance down the tube.

Adenosine Diphosphate↗