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Biomedical subjects

S Chien

Publications and source records attributed to S Chien.

At least 271 records · Page 15Linked to original sources

Direct relationship between blood pressure and blood viscosity in normal and hypertensive subjects. Role of fibrinogen and concentration.

Blood pressure and components of blood viscosity were measured in 49 normal subjects and in 49 untreated patients with essential hypertension. Blood viscosity values measured at six different shear rates were significantly correlated with blood pressure (r = 0.432 to 0.505, p less than 0.001). Blood viscosity was higher in hypertensive patients. This was due to both higher plasma viscosity (1.29 +/- 0.08 standard deviation versus 1.24 +/- 0.05 centipoise (cPs), p less than 0.001) and increased hematocrit values (44.4 +/- 4 percent versus 41.5 +/- 3 percent, p less than 0.005). When blood viscosity was evaluated in subgroups of normal and hypertensive subjects with matched hematocrit values, it remained higher in the hypertensive patients, and the relationship between blood pressure and viscosity was still significant. Regardless of the hematocrit value, fibrinogen levels were elevated in hypertensive patients (p less than 0.006) and, in association with the increased globulin concentration, fibrinogen was largely responsible for the increased plasma viscosity in hypertensive patients. Since the viscosity of defibrinated blood was similar in normal and hypertensive subjects with matched hematocrit values, the elevated fibrinogen level also affected whole blood viscosity. Defibrinated blood viscosity and arterial pressures were not correlated. These studies demonstrate a direct correlation between blood pressure and blood viscosity among normotensive and hypertensive subjects. This relationship is, in part, due to the rheologic effects of an elevated fibrinogen level and to an increased hematocrit value. The basis for hyperfibrinogenemia in hypertensive patients is unclear.

Adult↗

Passive mechanical properties of human leukocytes.

Micropipette experiments are used to determine the rheological properties of human leukocytes. Individual cells in EDTA are subjected to a known aspiration pressure via a micropipette, and their surface deformation from the undeformed spherical shape is recorded on a television monitor. The cells are mathematically modeled as homogeneous spheres, and a standard solid viscoelastic model is found to describe accurately the deformation of the cell for small strains. These experimental and theoretical studies provide the basis for further investigations of leukocyte rheology in health and disease.

Adult↗

Mechanics of Rouleau formation.

The formation of rouleau of red blood cells is considered from the standpoint of adhesion theory. With the use of the elastic properties of the red blood cell membrane obtained from previous work, the strain energy of the red blood cell in rouleau formation has been computed. The surface energy of adhesion for the bonding of two red blood cells is then computed from the variation of this strain energy. Computed cell shapes agree well with experiments.

Cell Adhesion↗

Colloidal gold--low density lipoprotein conjugates as membrane receptor probes.

We have developed a method for conjugating low density lipoproteins (LDL) with colloidal gold. Conjugation, complete after 1 min, occurs by electrostatic adsorption of the LDL to the negatively charged gold particle. Each conjugate consists of approximately eight biologically active LDL molecules clustered around a central 19-nm gold granule. Acidic (pH 4), alkaline (pH 9), or high ionic (600 milliosmolar NaCl) environments do not dissociate the conjugate. Colloidal gold is an electron-dense, nondegradable marker that is easily identified within the cell and serves as a valuable probe for studying receptor binding and endocytosis. By using a modified method of ruthenium red staining, the LDL molecules of the conjugate can be directly visualized when they are bound to the cell surface receptor. Receptor binding (4 degrees C) of the conjugate by cultured human fibroblasts reveals that the gold granule is positioned 18-21 nm from the coated pit region of the membrane. This distance, similar to the diameter of LDL, suggests concomitant internalization of the receptor during vesicular endocytosis and early lysosomal incorporation (10 min at 37 degrees C). Continued internalization (30-60 min at 37 degrees C) results in the formation of free pools of gold within the lysosome.

Cell Membrane↗

Hepatic binding and internalization of low density lipoprotein-gold conjugates in rats treated with 17 alpha-ethinylestradiol.

Receptor-mediated hepatic uptake of low density lipoproteins (LDL) conjugated to colloidal gold was studied by perfusion of livers from rats treated for 5 d with 17 alpha-ethinylestradiol. Estrogen treatment resulted in a marked decrease in serum lipid and lipoprotein concentrations. After 15 min of perfusion the conjugate was bound to the hepatic microvilli of both control and estrogen-treated rats; the estrogen-treated rats showed an 8- to 11-fold greater number of membrane-bound conjugates. The conjugates were bound to the membrane receptor by the LDL particle because the gold granules were regularly displaced from the membrane by 20 +/- 3.2 nm, the diameter of LDL. Internalization of the conjugate, evident by gold particles in multivesicular bodies, occurred at coated pits at the base of the microvillus where coated vesicles containing a single gold-LDL conjugate were released. After 1 h of perfusion, the livers from the estrogen-treated rats showed all phases of endocytosis and incorporation into multivesicular bodies of the conjugate. After 2 h of perfusion, there was congregation of gold-labeled lysosomes near the bile canaliculi. Gold-LDL conjugates were also observed to bind and be internalized by Kupffer cells and sinusoidal endothelium. These findings indicate that estrogen treatment induces hepatic receptors for LDL. The catabolic pathway of binding and endocytosis of the conjugate is similar to that seen in fibroblasts, although slower. Because gold-LDL conjugates were also present in the Kupffer and endothelial cells, the uptake of LDL by the liver involves the participation of more than a single cell type.

Animals↗

Bypass blood flow during carotid endarterectomy.

The relationship of bypass shunt blood flow to arterial pressure and stump pressure was studied in 12 informed patients undergoing carotid endarterectomy. These patients were anesthetized with halothane plus nitrous oxide. Systemic arterial blood pressure was measured with a radial artery catheter, and stump pressure as well as distal shunt pressure (carotid pressure distal to the shunt) were measured with a 25-gauge needle inserted cephalad to the bypass shunt. From the pressure drop across the bypass shunt, blood viscosity, geometry of the bypass tubing and the use of Poiseullie's law, the shunt blood flow can be calculated. The calculated shunt flow shows a close correlation with the difference between arterial pressure and stump pressure (r = 0.91) as well as with the slope of arterial pressure increase following carotid occlusion (r = 0.82); but it is poorly correlated with the stump pressure. Administration of 100 ml low molecular weight dextran solution does not improve the shunt blood flow, whereas 500 ml low molecular weight dextran significantly decreases blood viscosity. The patency of the carotid artery as assessed by angiogram does not give a proper indication of the need for a bypass shunt. The shunt flow as well as the need of such a shunt might be predicted by the use of the difference of arterial pressure and stump pressure. If the slope of arterial pressure increases rapidly following carotid occlusion, it can also be used to determine the necessity of such a shunt.

Adult↗

The design and use of a simple device for rapid quench-freezing of biological samples.

The detailed design of a simple device for rapid quench-freezing of biological samples under reproducible conditions is presented. With spring-augmented descent, sample immersion velocity of 10 m s-1 into a cryogenic liquid is achieved. Biological samples, loaded in Balzers planchets, Denton holders, or a newly designed 'titanium envelope', are suitable for rapid-freezing with this device. Using 4 micrometers titanium foil, light weight (1 mg) streamlined holders can easily be made to enclose cell suspensions or tissue samples. The foil envelope is designed for efficient heat dissipation while protecting the sample from possible impact or flow distortions occurring from spring-augmented immersion. Human erythrocytes, quench-frozen in the titanium envelope, were prepared for electron microscopy by the freeze-substitution technique. Two opposing 25--30 micrometers surface zones were frozen in the apparent absence of ice. The extended depth of cryofixation is attributed to the advantages of thin foil in the titanium envelope design and the use of rapid-immersion technique.

Erythrocytes↗

Vesicle transport in arterial endothelium and the influence of mechanical factors on macromolecular permeability.

The time-dependent transport of labeled vesicles in arterial endothelium has been modeled, taking into account the space-varying electrodynamic and hydrodynamic forces and the steric hindrance of vesicle attachment by the already attached vesicles. With the aid of laboratory model experiments to assess the steric hindrance effect, theoretical computation has been made on time-dependent labeled vesicle concentration profiles, and the results agree reasonably well with the published experimental data. Oscillatory length variations (5-10 Hz for 15 min) and elevation of transmural pressure (from 0-100 and 200 mmHg) caused increases in 125I-albumin uptake by the canine common carotid artery. Theoretical computations based on ultrastructural determination of free vesicle density indicate that there was negligible enhancement of vesicle diffusion by these mechanical disturbances. The increases in albumin uptake following length oscillation and pressure elevation to 100 mmHg were accompanied by increases in luminal surface area, and the albumin permeability remained unchanged. The albumin permeability was elevated following pressure elevation to 200 mmHg, and this was attributable to (a) a decrease in transendothelial diffusion distance, and (b) facilitation of vesicle loading into the vesicles.

Animals↗

Filterability and other methods of approaching red cell deformability. Determinants of blood viscosity and red cell deformability.

The major determinants of blood viscosity are RBC concentration, plasma viscosity, RBC aggregation and RBC deformation. RBC deformation is determined by the intrinsic deformability of the cell and the shear stress acting on the cell surface. In using filterability tests to assess RBC deformability, it is necessary to eliminate variations in other determinants of blood viscosity and to specify the rheological conditions of the test. Further theoretical and experimental work is needed for the interpretation of filterability tests in terms of cell geometry, internal viscosity and membrane properties.

Blood↗

The effects of mannitol on blood viscosity.

To determine the effect of mannitol on blood viscosity, serial measurements were carried out on venous blood in patients undergoing craniotomies for intracranial aneurysms. Blood samples were drawn immediately prior to, and 30 minutes, 2, and 4 hours after administration of mannitol. Complete blood counts, serum osmolarities, and erythrocyte microsieving studies were also performed on each sample. Whole-blood viscosity decreased at 30 minutes and 2 hours, but not at 4 hours after mannitol administration. This decreased appeared at high shear rates only, where erythrocyte deformability is critical viscosity. This effect was independent of the hematocrit. Removal of mannitol from the suspension returned red cell deformability to preadministration values indicating that the increased erythrocyte deformability required the presence of mannitol and the relative hyperosmolarity induced by this agent. The reduced erythrocyte rigidity and subsequent decreased whole-blood viscosity should enhance tissue perfusion in the microcirculation.

Blood Viscosity↗