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Biomedical subjects

S Chien

Publications and source records attributed to S Chien.

At least 253 records · Page 14Linked to original sources

Indices of filterability of red blood cell suspensions.

A number of different experimental techniques have been devised in recent years to use microsieving as a test of the filterability of suspensions of red blood cells. Various indices have been proposed to express the results of these tests. In the present paper a correlation is made of the intrinsic increase in resistance at the level of a single pore in the filter to the macroscopically observed pressure and flow through the entire filter. Further it is shown how a number of different tests may be used to derive the same index. The results apply only to situations in which there is no plugging of pores.

Erythrocytes↗

On the antithrombogenic action of low molecular weight heparins and of chondroitins A, B and C.

Hemorheological studies were made on surface layers of solutions of highly purified human fibrinogen, to which low molecular weight (LMW) heparins, as well as chondroitins A, B and C were added. The surface viscous (eta's) and elastic (Gs) moduli of these fibrinogen systems were measured with a modified Weissenberg Rheogoniometer. Our findings show that n's and Gs of these heparin-fibrinogen and chondroitin-fibrinogen surface systems were markedly decreased as compared to the fibrinogen control. Heparin of MW 4400 exhibited about 30 per cent decrease, while heparins of MW 5300 and 5900 had decreases of approximately 75 per cent in n's and Gs. The three chondroitins A, B and C were found to reduce the n's and Gs by about 40 per cent. The surface layers of fibrinogen, which are surface gels, constitute the clotting of fibrinogen without thrombin participation. Such so-called 'fibrinogenin' formation is considered by Copley to initiate thrombosis. The LMW heparins and the chondroitins tested, which we found to inhibit fibrinogen formation, may therefore be expected to act as antithrombotic agents. Thus, LMW heparins and chondroitins A, B and C may play important roles in the prevention of thrombosis.

Chondroitin↗

Sinusoidal endothelial endocytosis of low density lipoprotein-gold conjugates in perfused livers of ethinyl-estradiol treated rats.

We examined endocytosis of low-density lipoproteins (LDL) conjugated to colloidal gold by the sinusoidal endothelium in perfused livers of 17 alpha-ethinyl estradiol-treated rats. After 15 min of perfusion, the gold-LDL was randomly bound at the endothelial surface, but internalized only at coated pits. Uptake of the conjugate was to electron-lucid vacuoles. After 1 h of perfusion, there was a progressive accumulation of gold in organelles resembling lysosomes, with further accumulation seen at 2 h perfusion. Uptake of the conjugate was equivalent to the rate of 125I-LDL and competitively inhibited by a 20-fold excess of free LDL. These results suggest that a specific endocytotic pathway for LDL is present in the sinusoidal endothelium in the estrogen-hypolipidemic state.

Animals↗

Viscoelastic behavior of erythrocyte membrane.

A nonlinear viscoelastic relation is developed to describe the viscoelastic properties of erythrocyte membrane. This constitutive equation is used in the analysis of the time-dependent aspiration of an erythrocyte membrane into a micropipette. Equations governing this motion are reduced to a nonlinear integral equation of the Volterra type. A numerical procedure based on a finite difference scheme is used to solve the integral equation and to match the experimental data. The data, aspiration length vs. time, is used to determine the relaxation function at each time step. The inverse problem of obtaining the time dependence of the aspiration length from a given relaxation function is also solved. Analytical results obtained are applied to the experimental data of Chien et al. 1978. Biophys. J. 24:463-487. A relaxation function similar to that of a four-parameter solid with a shear-thinning viscous term is proposed.

Animals↗

Influence of physicochemical factors on rheology of human neutrophils.

The effects of variations in temperature, pH, and osmolality on the rheological properties of human neutrophils were determined by studying the cell deformation in response to aspirational pressure applied via a micropipette. The time history of the deformation was analyzed by the use of a standard solid viscoelastic model consisting of an elastic element K1 in parallel with a Maxwell element (an elastic element K2 in series with a viscous element mu). With changes in temperature over a range of 9-40 degrees C, only mu varied inversely with temperature, while K1 and K2 did not show significant alterations. Variations in pH over the range of 5.4-7.8 did not significantly affect the viscoelastic coefficients, but K1 and mu rose at pH 8.4. An increase in osmolality caused all three coefficients to rise, but a decrease in osmolality had relatively little effect on the coefficients. These changes in response to physicochemical variations serve to provide insights into the viscoelastic properties of neutrophils and their possible roles in health and disease.

Adult↗

Baroreflex control of heart rate in humans during nitroprusside-induced hypotension.

The baroreflex control of heart rate was investigated on 10 informed human subjects during light halothane anesthesia (0.3-0.5%, inspired concentration). The relationship of systolic pressure (SP) to the succeeding pulse interval (PI) was evaluated on a beat-to-beat basis during the entire course of sodium nitroprusside (SNP) depressor test. The initial slope of SP-PI plot (dPI/dSP) was used as an index of the sensitivity of baroreflex control of heart rate. Following an injection of SNP (4-6 micrograms/kg), dPI/dt was related directly to dPI/dSP, whereas the latter was inversely correlated with dSP/dt. The recovery of PI lagged behind that of SP, and there was a hysteresislike loop on the SP-PI plot. The time lag of PI recovery and the loop of SP-PI plot were markedly decreased by propranolol treatment and significantly increased by atropine. The slopes of SP-PI plot were significantly decreased by atropine but relatively unaffected by propranolol. These results indicate that SNP-induced hypotension in man during halothane anesthesia is associated with a withdrawal of parasympathetic inhibition and an enhancement of sympathetic activity. The autonomic control of heart rate in response to rapid changes in arterial pressure induced by SNP is dominated by parasympathetic influence; the more persistent sympathetic activity only becomes evident when the parasympathetic influence subsides quickly as the arterial pressure stays relatively constant at a new level. The slope of SP-PI plot (dPI/dSP) and the ratio of dPI/dt to dSP/dt during the decreasing pressure phase of SNP test can be used as indices for the sensitivity of baroreflex control of heart rate.

Adult↗

A new method for kidney perfusion in situ: application to dynamics of autoregulation.

A procedure for in situ perfusion of kidney was developed in which renal resistance does not rise with continued perfusion at a constant rate and renal blood flow (RBF) can be changed as a step function. The kidney of dogs anesthetized with pentobarbital-chloralose was perfused by a pulsatile syringe pump via an extracorporeal circuit placed between the femoral artery and the renal artery. The perfusion pressure and pulse rate can be adjusted to match those of the dog. Following a step change in RBF from the control level, the dynamics of the autoregulatory response was studied by determining the time course of the alteration in renal perfusion pressure as RBF was maintained at the new constant level. An increase in RBF led to a time-dependent renal vasoconstriction (increase in renal resistance), and a decrease in RBF caused a time-dependent renal vasodilation (decrease in renal resistance). The time course of the response of renal resistance to step changes in RBF can be described by monoexponential functions. The time constant obtained for resistance changes after both an increase and a decrease in RBF was 37.5 +/- 2.8 (SD) s. During the period of step recovery from changes in RBF in either direction, the time constant of the renal resistance response was 53.4 +/- 3.2 s. These values are useful for the analysis of the mechanism of renal autoregulation as well as the modeling of circulatory and hormonal control. The results also indicate that this new procedure for renal perfusion in situ is well suited for studying renal hemodynamics and other functions.

Animals↗

Rheology of blood cells as soft tissues.

Erythrocytes are unusual in that the cell membrane plays a large and direct role in observed rheological properties. The cell membrane is not a three dimensional material or tissue in the usual sense but being only two molecules thick. It behaves like a liquid sheet of constant thickness and surface area with some elastic properties due in part to protein networks of spectrin and actin on the interior face of the cell membrane. Packed red cells form a viscoelastic fluid which can be sheared, but exhibits a considerable elastic response. The elastic component decreases as the hematocrit is reduced, but is present at all hematocrits. Leukocytes also exhibit viscoelasticity but the properties are primarily dependent on the cell cytoplasm. The cell membrane plays a role only when it is stretched taut. The normal white cell properties have been explored over a wide range of osmolarities, becoming much less viscous and less elastic as the fluid content of the cell increases. White cells also may show spontaneous deformation during which the rheological properties become much stiffer than in the normal passive state.

Biomechanical Phenomena↗

Human SS red cell rheological behavior in the microcirculation of cremaster muscle.

The hemodynamic behavior of Hb SS erythrocytes introduced into the microcirculation of cremaster muscle (rat and mouse) was studied by intravital microscopy. Simultaneous measurements of intravascular pressure, pressure drop, red cell velocity, hematocrit and oxygen tensions were made to evaluate both regional resistance (arteriovenous) from 2nd order arterioles to venules, as well as the resistance to blood flow in single unbranched arterioles. Following the isovolemic exchange of 2 to 3 blood volumes with SS cells at 25% hematocrit, regional resistance remained within 20% of its control value due to compensatory vasodilation and shunting of blood through pathways parallel to capillaries occluded by sickled red cells. Prolonged exposure to circulating SS cells resulted in a degradation of microvascular function with an attendant four-fold rise in regional resistance. Transient resistance measurements during the passage of a bolus of SS cells through the cremasteric network demonstrated a 100% increase in regional resistance, which was rapidly abated by the subsequent SS cell washout and capillary recruitment. Computations of apparent viscosity in single unbranched arterioles (nominal diameter of 45 micrometer) revealed a four-fold rise in viscosity following the reduction in intravascular oxygen tension (PO2) from 40 mm HG to 7 mm Hg. Observations on the transient increase in viscosity concomitant with a rapid decrease in PO2, demonstrated a lag time of 2 to 3 s before the elevation of viscosity. To enhance the visualization of these processes, techniques for the fluorescent labelling of Hb SS cells with fluorescein isothiocyanate (FITC) were applied. Visual observations of the movement of SS-FITC red cells by fluorescence microscopy readily revealed the sequestration of sickled cells at the junction between 10 micrometer transverse arterioles and the smaller true capillaries, and the shunting of labelled cells around obstructed capillaries.

Abdominal Muscles↗

Correlation of hemodynamics in macrocirculation and microcirculation.

The current state of our understanding on the correlation between hemodynamics in the micro- and macrocirculation is assessed. The use of microcirculatory approach has allowed the identification of the sites of microvascular responses to neuro-humoral influences which are known to affect the overall resistance determined by macrocirculatory experimentation. Direct determinations of hematocrit and apparent viscosity in microvessels have helped to interpret macrocirculatory findings on the distribution of red cells and plasma and on the pressure-flow relationships in normal and pathological conditions. Hemodynamic measurements made on microvessels in the ventricular epicardium have provided the microcirculatory bases of the variations in coronary blood flow during the cardiac cycle and the changes in coronary hemodynamics in response to vasodilators. Microcirculatory studies on the surface glomeruli of Munich-Wistar rats have allowed the identification of the sites of microvascular actions of vasoactive agents and the determination of their effects on glomerular filtration coefficient. Several attempts have been made to synthesize the overall hemo-dynamics at the organ level from microcirculatory data, with some degree of success. In order to attain the goal of correlating macrocirculatory and microcirculatory hemo-dynamics, we need to perform parallel investigations at these levels on the same organs or tissues in the same animal species, together with morphological characterization of the microcirculatory architecture and theoretical modeling in which accounts are taken of the heterogeneity of structural and functional parameters.

Animals↗

Viscoelastic properties of sickle cells and hemoglobin.

The quantitative relationship between deoxygenation and rheological behavior of SS cell suspensions and concentrated HbS solutions has been studied under steady shear (viscosity eta) and oscillatory shear (complex viscosity with viscous component eta' and elastic component eta"). decrease of O2 saturation below 80-85% causes eta, eta' and eta" to increase progressively in SS cell suspensions and HbS solutions. These rheological parameters do not change in AA cell suspensions and HbA solutions following deoxygenation. The deoxygenation-induced increase in eta" of HbS solutions from the unmeasurable level when oxygenated reflects the gelation of HbS. At high O2 saturations, the rheological behavior of the intracellular fluid has relatively insignificant contribution to that of the SS cell suspension. As O2 saturation decreases, the viscoelastic properties of the SS cell suspension become increasingly dominated by that of the intracellular HbS. at a given degree of deoxygenation, eta, eta' and eta" of HbS solutions decrease with increasing shear rate, indicating that HbS aggregates can be dispersed by shear stress.

Anemia, Sickle Cell↗

Rheology in the microcirculation in normal and low flow states.

A brief review is given for the rheological behavior of blood in the microcirculation in normal and low flow states. Blood viscosity increases in low flow conditions because of the decrease in shear stress which normally causes red cell deformation and disaggregation. The low hematocrit found in the microvessels leads to a decrease in apparent blood viscosity and tends to compensate for the high vascular hindrance due to the narrowness of the vessels. The presence of the less deformable white blood cells in the microcirculation causes a retardation of red cell flux and a redistribution of red cells at bifurcations. Elevated hematocrit, in turn, can cause an enhancement of the interaction between white blood cells and the venular endothelium. Adhesion of white blood cells to microvascular endothelium leads to an increase in flow resistance, especially in low flow states. The optimum hematocrit for myocardial oxygen transport and utilization is shifted from near 40% in normal conditions to 25% in hemorrhagic hypotension. These findings indicate that blood rheology in the microcirculation should be considered in analyzing the pathophysiological disturbances in shock and that improvement of microcirculation rheology offers a promising approach in treatment.

Biological Transport↗

Oxidation of ruthenium red for use as an intercellular tracer.

When ruthenium red (RR) is combined with OsO4, an electron-opaque complex forms which readily binds to the cell surface coat. However, the RR-OsO4 complex is often excluded from intercellular spaces in many cell types, and thus is not dependable as a tracer of regions continuous with the extracellular space. Postfixation of erythrocytes agglutinated by the lectin helix (Helix promatia) and intact carotid artery endothelium with a freshly prepared mixture of 1% OsO4 containing 0.1% ruthenium red (RR) resulted in a dense surface deposit of these cells, but intercellular regions were penetrated to a minimal degree by the stain. When a similar mixture of RR-OsO4 was allowed to stand 3 h before use, RR is oxidized by OsO4 to yield a ruthenium compound that has a spectrophotometric absorbance maximum at 365 nm. This RR molecule has a reduced number of cationic sites due to binding with osmium dioxide OsO2=. Postfixation of agglutinated RBCs and carotid artery endothelium with this oxidized ruthenium-OsO4 mixture resulted in a 50-80% decrease in surface deposition but markedly enhanced penetration into intercellular regions. The enhanced penetration is attributed to decreased binding affinity of the oxidized ruthenium for anionic surface membrane components, permitting effective stain penetration of cell-to-cell contact rather than extensive surface deposition. These studies indicate that the ruthenium compound formed by OsO4 oxidation of ruthenium red may be a useful tracer for ultrastructural visualization of intercellular spaces and junctions.

Animals↗