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Biomedical subjects

S Chien

Publications and source records attributed to S Chien.

At least 145 records · Page 8Linked to original sources
PubMed1990

Effects of blood viscosity on renin secretion.

The effects of alterations in blood and plasma viscosities on plasma renin activity (PRA) were studied in dogs anesthetized with pentobarbital. Blood viscosity was altered by changing the hematocrit (Hct) level by isovolemic exchange using packed red blood cells or plasma. Plasma viscosity was elevated by isovolemic exchange using Hct-matched blood with high molecular weight dextran (Dx, mean m.w. approximately 450,000) dissolved in plasma. Following control measurements of plasma and blood viscosities, plasma [Dx], PRA, Hct and hemodynamic functions, the dog was subjected to isovolemic exchange transfusions to either alter the Hct or administer the Dx. Various measurements were repeated 40-60 min after each exchange. Arterial pressure and renal blood flow remained relatively constant after exchanges; increases in plasma and blood viscosities were accompanied by a decrease in renal vascular hindrance (vasodilation) to keep the renal flow resistance at control level. PRA rose with increases in plasma [Dx] and viscosity, and the rise in PRA was best correlated with the decrease in renal hindrance. The changes in PRA and renal hindrance have the same regression line whether blood viscosity was altered by Hct variation or Dx administration. The results indicate that increases in viscosity cause a compensatory vasodilation of renal vessels to cause renin secretion.

Animals↗
PubMed1989

Velocity distribution on the membrane of a tank-treading red blood cell.

The kinematics of an area-conserving tank-treading disk-shaped red blood cell membrane is studied using the stream function method suggested by Secomb and Skalak (Q. Jl Mech. appl. Math. 35, Pt 2, 233-247, 1982). Two simple area-conserving velocity fields are superimposed to satisfy the continuity condition at the curved edges of the disk. A differential equation for the trajectory of any material point of the membrane is derived. The requirement of synchrony of the cycle for all membrane points leads to an integral equation which determines a magnitude function. An approximate solution is made possible by assuming small trajectory deflections.

Biomechanical Phenomena↗
PubMed1989

Eighteen to 37 hours' preservation of major organs using a new autoperfusion multiorgan preparation.

A new autoperfusion preparation was used to preserve six major organs simultaneously. In 7 Yorkshire white swine, the heart and lungs were separated and removed with the liver, pancreas, duodenum, and both kidneys en bloc while they were self-perfused. Fresh blood, glucose, electrolytes, heparin sodium, methylprednisolone, and a fat emulsion (Soyacal) were infused through the portal vein. No inotropic drugs were necessary. The organs survived for 18 to 37 hours (average survival, 24.6 +/- 2.7 hours [+/- standard error of the mean]). Aortic systolic pressure ranged from 78.5 +/- 5.5 to 98.7 +/- 11.8 mm Hg. Arterial oxygen tension ranged from 206 +/- 23 to 266 +/- 15 mm Hg and arterial carbon dioxide tension, from 20.1 +/- 2.7 to 32.1 +/- 4.9 mm Hg. Blood lactic acid levels decreased from 8.75 +/- 2.06 to 5.50 +/- 2.45 mmol/L at 24 hours. Urine output ranged from 25 to 82 mL/h. Blood urea nitrogen levels decreased from 9.17 +/- 0.59 to 4.67 +/- 1.08 mg/dL. Blood creatinine levels decreased from 1.34 +/- 0.10 to 0.57 +/- 0.22 mg/dL. Serum glutamicoxaloacetic transaminase levels increased from 73.4 +/- 26.3 to 194 +/- 179.5 U/L and serum glutamic-pyruvic transaminase levels, from 44.8 +/- 5.7 to 91 +/- 66.4 U/L. Red blood cell count ranged from 6.94 +/- 0.58 to 13.23 +/- 2.30 x 10(6)/microliters. Lung wet/dry weight ratios changed from 5.79 +/- 0.17 at the beginning to 6.25 +/- 0.16 at 24 hours. The technique for simultaneous multiorgan preservation presented here is simple, effective, and highly reproducible. This study appears to have produced one of the longest average survival times for autoperfusion.

Animals↗
PubMed1989

Theoretical and experimental studies on cross-bridge migration during cell disaggregation.

A micromanipulation method is used to determine the adhesive energy density (gamma) between pairs of cytotoxic T cells (F1) and their target cells (JY: HLA-A2-B7-DR4,W6). gamma is defined as the energy per unit area that must be supplied to reduce the region of contact between a conjugated cell pair. Our analysis of the data indicates that the force applied by the micropipette on the cell is not uniformly distributed throughout the contact region as we had previously assumed (Sung, K. L. P., L. A. Sung, M. Crimmins, S. J. Burakoff, and S. Chien. 1986. Science (Wash. DC). 234: 1405-1408), but acts only at the edges of the contact region. We show that gamma is not constant during peeling but increases with decreasing contact area of the conjugated cell pairs F1-JY, F1-F1, and JY-JY in contrast to the constancy of gamma for typical engineering adhesives. This finding supports the notion that the cross-linking protein molecules slide towards the conjugated area across the leading edge of the separation while remaining attached to both cells. Our mathematical analysis shows that the elastic energy stored in the cross-links by the membrane tensions balances the diffusive forces that act against cross-bridge migration. The binding affinity between F1-JY is found to be approximately 15-20 times larger than the corresponding affinity for F1-F1. The number of binding sites of F1 for attachment to JY is approximately the same for binding F1 to another F1 and vary between 10(5) and 10(6).

Animals↗
PubMed1989

Role of leukocyte-endothelium adhesion in affecting recovery from ischemic episodes.

The role of the inflammatory process in the onset of sickle cell crisis has not been fully elucidated, although there is evidence for leukocytosis and enhanced leukocyte to endothelium adhesion. The elevated LEA typical of inflammation may impede recovery from transient ischemic episodes by increasing the resistance to blood flow, which in the case of sickle cell disease may exacerbate the "vicious cycle" of HbS deoxygenation which leads to microvascular stasis. Recent studies on the mechanics of white blood cell margination and adhesion in postcapillary venules of laboratory animals, either in the low-flow state or following tissue exposure to chemoattractants, reveal a marked rise in intravascular resistance with LEA. Such increases may be as great as twofold with as few as 6 WBCs adhering per 100 microns of venule length. In human subjects, leukocytosis attendant to crisis has been correlated with increased time to recover from induced periods of ischemia in skin capillaries. Thus, further definition of the role of the inflammatory process in crisis is needed in light of microvessel obstruction in the low-flow state.

Anemia, Sickle Cell↗
PubMed1989

Effects of dextran-induced hyperviscosity on regional blood flow and hemodynamics in dogs.

In 10 pentobarbitalized dogs, plasma viscosity (Ep) was raised fourfold while apparent blood viscosity (Ea) increased about twofold by two steps of exchange transfusion of 200 ml of plasma with plasma containing high molecular weight dextran (mol wt 500,000, 20% wt/vol). Elevation of Ea was primarily caused by an increase of Ep but not red cell aggregation. As Ea increased, regional blood flow (by 15-microns microspheres) remained constant in most organs but reduced in the small intestine, spleen, and thyroid gland. Vascular hindrance (Z), which reflects the state of vascular geometry, was calculated as flow resistance per Ea. Among various organs, a reduction in Z was noted in the heart, liver, pancreas, kidney, brain, and adrenal gland. In myocardium, there was a progressive reduction of the endocardial-to-epicardial flow ratio, indicating a less profound vasodilation in endocardium than epicardium. These results indicate that dextran-induced hyperviscosity leads to a compensatory vasodilation in several vital organs thus serving to maintain blood flow and nutrient transport.

Animals↗
PubMed1989

Salt-induced hypertension in Dahl salt-sensitive rats. Hemodynamics and renal responses.

This study was performed with Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats to detect differences in cardiovascular hemodynamics and renal responses that might be involved in initiating salt-induced hypertension in DS rats. The effects of 4 weeks of 8% NaCl diet were studied in conscious, male DR and DS rats in which vascular and urinary catheters had been previously implanted. Results were compared with those obtained from control groups of DR and DS rats on 4 weeks of 1% NaCl diet. DR rats on 8% salt diet did not develop hypertension, and cardiac output and blood volume were unchanged; glomerular filtration rate, urinary flow, sodium excretion, and plasma atrial natriuretic factor (ANF) increased. DS rats on 8% salt diet developed hypertension, and cardiac output and blood volume increased; glomerular filtration rate, urinary flow, and sodium excretion did not change, despite an increase in ANF. DS and DR rats on 1% NaCl diet were subjected to ANF infusion. After ANF infusion DR rats had a decreased blood volume and an increased glomerular filtration rate, urinary flow, and sodium excretion; DS rats showed no significant changes in blood volume, glomerular filtration rate, urinary flow, or sodium excretion. ANF caused vasodilation in all regions studied in DR rats; DS rats showed vasodilation in all regions except the kidney. After acute volume expansion, although both DR and DS rats responded by an increase in cardiac output, only DS rats developed prolonged hypertension. This finding suggests an inadequate vasodilatory mechanism in DS rats. In response to acute volume expansion, renal resistance decreased in DR rats but not in DS rats. It is concluded that the primary hemodynamic disturbance in DS rats with salt-induced hypertension is an increase in cardiac output caused by blood volume expansion in the absence of any vasodilation. Comparison of the responses of DS and DR rats to high salt diets, ANF infusion, and acute volume expansion indicates that the salt-induced hypertension in DS rats is initiated by a diminished renal response to ANF.

Animals↗
PubMed1989

Effect of nimodipine on cerebral blood flow and metabolism in rats during hyperventilation.

Nimodipine shws promise in the prevention and treatment of brain ischemia. We examined the interaction of nimodipine pretreatment in a dose sufficient to prevent postischemic hypoperfusion and hyperventilation. We studied four groups of rats: normocarbia plus vehicle (Group 1, n = 5), hypocarbia plus vehicle (Group 2, n = 4), normocarbia plus nimodipine (Group 3, n = 7), and hypocarbia plus nimodipine (Group 4, n = 6). Groups 3 and 4 received 1 mg/kg i.p. nimodipine, and Groups 1 and 2 received an equivalent amount of vehicle. Ventilation was left unaltered in Groups 1 and 3 or increased to lower PaCO2 to 21-24 mm Hg in Groups 2 and 4. Determination of regional cerebral glucose utilization (rCGU) was carried out using the [3H]2-deoxyglucose method, and regional cerebral blood flow (rCBF) was determined by the indicator fractionation method using [14C]iodoantipyrine. The brain regions studied were the cerebral hemispheres, the diencephalon, the cerebellum, and the brainstem. Hyperventilation in Groups 2 and 4 from approximately 38 to 22 mm Hg reduced rCBF to 60% of normocarbic levels (p less than 0.05). The slope and intercept of this response were similar in vehicle- and nimodipine-pretreated rats. Nimodipine modestly decreased mean arterial blood pressure by 20% and increased plasma glucose concentration by 60% (p less than 0.05). Although nimodipine tended to increase rCBF and decrease regional cerebrovascular resistance (rCVR), this was significant only for hemispheric rCVR (p less than 0.05). There was a borderline effect for nimodipine to increase rCGU, especially during hypocarbia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of centrifugation on transmembrane water loss from normal and pathologic erythrocytes.

Plasma 125I-albumin was used as a marker of extracellular dilution in order to study the effect of high-speed centrifugation on transmembrane water distribution in several types of human red cells, including normal (AA), hemoglobin variants (beta A, AS, SC, beta S, and SS), and those from patients with hereditary spherocytosis. SS and AA erythrocytes were also examined for changes in intracellular hemoglobin concentration of three different density fractions and with increasing duration of spin. The minimum force and duration of centrifugation required to impair water permeability were found to vary with the red cell type, the anticoagulant used (heparin or EDTA), the initial hematocrit of the sample centrifuged, as well as among the individual erythrocyte fractions within the same sample. When subjecting pathologic erythrocytes to high-speed centrifugation, the 125I-albumin dilution technique can be used to determine whether the centrifugation procedure has led to an artifactual red cell water loss and to correct for this when it does occur. An abnormal membrane susceptibility to mechanical stress was demonstrated in erythrocytes from patients with hereditary spherocytosis and several hemoglobinopathies.

Anemia, Sickle Cell↗
PubMed1989

Shear stress-induced detachment of human polymorphonuclear leukocytes from endothelial cell monolayers.

We employed a static-incubation assay to determine the intensity of wall shear stress (tau) needed to detach human polymorphonuclear leukocytes (HPMNs) from human umbilical vein endothelial cell (HUVE) monolayers. Confluent monolayers of HUVE were placed in a parallel-plate flow chamber which was mounted on the stage of an inverted tissue culture microscope, attached to a perfusion system and maintained at 37 degrees C. All events in the selected fields were recorded using videomicroscopy. HPMNs were co-incubated for 15 minutes with the HUVE monolayers under control conditions or in the presence of 10(-7) M formyl-methionyl-leucyl-phenylalanine (FMLP). Following this static incubation, a series of five individual flows, each 1 minute in duration, were driven through the flow channel, exposing the cells to 1.0, 2.0, 3.8, 7.6 and 14.8 dyn/cm2 wall shear stresses. Under control conditions, the percentage of HPMNs remaining attached to the HUVE monolayers following exposure to each shear stress was 61, 38, 25, 12 and 5, respectively. In the FMLP-treated condition, the percentage of HPMNs remaining attached to the monolayers was significantly greater than control at all five levels of tau. Thus, under control conditions, adherent HPMNs can be detached from endothelial cell monolayers in vitro with levels of shear stress normally found in the microcirculation (18). In the presence of FMLP, the level of shear stress needed to overcome the adhesions is increased significantly.

Cell Adhesion↗
PubMed1989

Erythrocyte sedimentation realizable in terms of population dynamics.

A phenomenological theory is formulated in analogy to the theory of population dynamics to account for the observed erythrocyte sedimentation-time and velocity-time curves. The least square fitting of experimental data to the derived equations is quite satisfactory. Several parameters in the proposed equations can be used to characterize these two curves of erythrocyte sedimentation: the biotic potential or intrinsic rate of decrease of the lacuna population, r; the total distance settled by the interface between plasma and red cell column, K.delta h; the maximal settling velocity of the interface, Vmax; the time when Vmax occurs, tmv; and the final position of the interface, Hf.

Blood Sedimentation↗
PubMed1989

Filtration of sickle cells: recruitment into a rigid fraction as a function of density and oxygen tension.

The rheologic behavior of sickle cells was evaluated with a constant flow filtration system at 37 degrees C by using filters with pores of 4.8 microns diameter. Analysis of the shape of the pressure-time curves suggested that sickle cells were subdivided into two discrete subpopulations: (1) relatively deformable cells and (2) cells so rigid that they plugged the pores. The analysis allowed calculation of the fraction of cells causing plugging (FP), even when FP represented less than 0.01% of the population. FP rose with falling Po2 level, apparently with the recruitment of progressively less dense cells into the plugging fraction. A density profile for each sample was constructed. When we made the assumption that the plugging cells represented the denser moiety, this profile allowed identification of the threshold Po2 level at which cells of a given density, deoxygenated under these conditions, became unable to traverse the 4.8 microns pore.

Anemia, Sickle Cell↗
PubMed1989

An animal study of portal hypertension.

For the purpose of elucidation the mechanism of portal venous resistance and portal venous blood flow in maintaining an elevated portal hypertension. The splanchnic and systemic hemodynamics were evaluated in portal hypertensive rat model, which is induced by partial portal vein ligation (PVL). Organ blood flow and portal-systemic shunting were measured by radio-active microsphere techniques. In this study all the PVL rats had higher mean portal venous pressure (15.2 +/- 1.6 mmHg) when compared to the Sham-operation control rats (5.3 +/- 1.2 mmHg). Furthermore, portal systemic shunting was significantly higher in the 14th day PVL rats (87.2 +/- 3.6%) than control rats (0.3 +/- 0.1%) (p less than 0.05). There was a rapid increase in portal venous inflow from the 4th day (6.1 +/- 0.8 vs 4.2 +/- 0.7 ml/min/100 gm BW, p less than 0.05) in the PVL rats than in control rats. However, the total peripheral resistance and splanchnic arterial resistance were reduced in the 14th PVL rats than control rats. The Cardiac index was much higher in the 14th PVL rats than control rats. Thus our results demonstrate that portal hypertension is maintained by a hyperdynamic portal venous inflow. This model is reproducible for us to study portal hypertension within a short period of time.

Animals↗
PubMed1989

Viscoelastic properties of red cell membrane in hereditary elliptocytosis.

The viscoelastic properties of the RBC membrane are in part determined by a submembrane network of proteins consisting of spectrin alpha beta heterodimers (SpD) assembled head-to-head to form spectrin tetramers (SpT) and spectrin oligomers (SpO). SpT, in turn, are connected into a two-dimensional network by the linkage of distal ends of SpT to protein 4.1 and actin. With the micropipette technique, we determined the membrane viscoelastic properties of RBCs from a subset of patients with hereditary elliptocytosis (HE); these RBCs exhibit membrane skeletal instability, defective SpD self-association, and a molecular defect in the alpha I domain of spectrin, which is involved in the SpD-SpD contact (HE SpD alpha-SpD). The elastic modulus and viscosity of the membrane were significantly higher for the HE RBCs than for the control cells. Incubation of normal cells with N-ethyl-maleimide (NEM) produced a similar defective SpD self-association and a significant increase in the viscoelastic parameters of the membrane. The data provide evidence that the mode of assembly of membrane spectrin in the cytoskeletal protein network plays a major role in determining the rheologic behavior of erythrocyte membrane.

Elasticity↗
PubMed1988

On the time dependent diffusion of macromolecules through transient open junctions and their subendothelial spread. 2. Long time model for interaction between leakage sites.

In Part 1 of this study (Weinbaum et al., 1988) a short time model has been proposed to describe the initial time dependent leakage of macromolecules at short distances (5 microns or less) from the exit of a transient open junction which the authors have hypothesized as a characteristic feature of endothelial cells in the process of turnover (Weinbaum et al., 1985). This open junction pathway has also been proposed (Weinbaum et al., 1988) to be the primary ultrastructural correlate of the 20 nm diameter large pore suggested by Renkin et al. (1977) using the predictions of cylindrical pore theory. The short time model in (Weinbaum et al., 1988), however, has major limitations in that it neglects the interaction between leakage sites, macromolecular entry through other pathways, the finite thickness of the vessel wall and the curvature of the cell perimeter. The longer time model developed herein will attempt to describe each of these features and also present an improved model and analytic solution for the steady state flux and uptake. In the previous steady state model developed by Weinbaum et al. (1985) the effect of the resistance of the transient open junctions and the non-isotropic diffusion in the underlying tissue due to the internal elastic lamina (IEL) were both neglected. New solutions are first presented which describe the effect of these important model refinements on the steady state macromolecular permeability of the major arteries. Time dependent solutions are then presented to predict the transient longer time labeling following the introduction of tracer macromolecules of varying size. These solutions and the corresponding short time solutions in Weinbaum et al. (1988) are the first solutions to our knowledge to describe the difficult time-dependent boundary value problem to determine how the channel exit concentration and flux at a leaky junction vary with time. This is accomplished by casting the boundary value problem in the form of an integral equation for the unknown flux at the cleft exit and then solving this problem using a specially designed numerical technique. The theoretical predictions are used to interpret the behavior of the localized leaks to HRP and albumin that have been reported in Stemerman et al. (1986) and our own recent experiments (Lin et al., 1988).

Animals↗
PubMed1988

On the time-dependent diffusion of macromolecules through transient open junctions and their subendothelial spread. I. Short-time model for cleft exit region.

In this two-part study we shall quantitatively study, using time-dependent models, the hypothesis that transient open junctions associated with widely scattered endothelial cells undergoing mitosis are the structural equivalent for the large pore pathway via which macromolecules the size of albumin or larger cross the vascular endothelium. In an earlier steady-state model [Am. J. Physiol. 248, H945-960 (1985)], the authors demonstrated that such an open-junction pathway could quantitatively account for the regional differences in macromolecular permeability observed in various mammalian arteries in regions of enhanced cell turnover as indicated by 3H-thymidine although these cells were less than 1% of the population and the open junctions occupied less than 10(-5) of the endothelial surface. The time-dependent models described herein have been used to identify a time window and size of probe molecule wherein this hypothesis could be tested experimentally in the larger blood vessels. The first stages of these experiments have now been completed and provide convincing evidence that the junctions of virtually all endothelial cells in the M phase of the cell cycle are leaky to macromolecules (Lin et al., 1988). The statistical frequency of such leakage sites has also been determined. The time-dependent models developed herein contain two important refinements that were not contained in the earlier steady state model. First the finite resistance of the open cleft as a function of molecular size is accounted for by introducing a diffusion coefficient ratio Dj/Dz describing the relative resistance of the open cleft compared to the subendothelial tissue in the direction normal to the endothelial surface. Second the non-isotropy of the vessel wall due to the elastic lamina is considered by introducing a second diffusion coefficient ratio Dx/Dz describing the relative resistance in the lateral as compared to the normal direction. This second ratio can be as large as 100 for the arterial intima, but is of order unity for capillaries. In Part I a short time model is presented to describe the initial labeling of the open cleft and the subendothelial space in the vicinity of the cleft exit following the introduction of a tracer macromolecule. This model is valid for both larger vessels and capillaries since wall thickness and curvature and the interaction between leakage sites does not enter into the model description. In Part II (Wen et al., 1988) a long-time model is developed for larger vessels only which is valid for greater times including steady-state labeling.

Albumins↗