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Biomedical subjects

I A Feuerstein

Publications and source records attributed to I A Feuerstein.

At least 37 records · Page 2Linked to original sources

Platelet accumulation on collagen: drugs which inhibit arachidonic acid metabolism and affect intracellular cyclic AMP levels.

We have studied the accumulation of washed platelets on collagen-coated glass from flowing platelet-red blood cell suspensions in the presence and absence of drugs. Glass tubes were 10 cm long and the flow rate was 1 ml/min, 80 s-1. For all experiments, platelet accumulation was greatest near the tube's inlet with a continuous decrease to the exit. A common feature, of those drug treatments which lead to reduced accumulation at the inlet, was an increase in outlet accumulation when compared with outlet control values. Platelet-collagen adhesion resulted in maximal release of 3H-serotonin in the presence of agents that prevent platelet aggregation on collagen. Only drug treatment known to raise cAMP levels (PGE1 and dipyridamole) or prevent the formation of prostaglandins and thromboxanes (sulfinpyrazone, indomethacin and ASA) were found to inhibit aggregate growth. Platelet aggregation on collagen in the absence of thrombin likely proceeds through the liberation of prostaglandins and thromboxanes from surface-bound platelets into the flow where they may stimulate flow-born cells. An alternate hypothesis is that such treatments affect the release of alpha-granule components necessary for aggregation.

Alprostadil↗

Adhesion and aggregation of thrombin prestimulated human platelets on surface-bound fibrinogen: evidence for involvement of ADP and arachidonic acid pathways.

The purpose of this study was to examine the influence of substances released from human platelets upon their accumulation on human fibrinogen-coated glass tubes. After prestimulation with thrombin for one minute or in the absence of prestimulation, washed human platelets suspended in Eagle's medium with RBC were drawn through the tubes at 1 ml/min, 80 s-1, for 1, 2 or 6 min. Thrombin prestimulation (0.02, 0.05 or 0.25 U/ml) was followed by inactivation with hirudin (0.1, 0.25 or 1.25 U/ml) before flow. Singly adherent platelets were observed in the absence of thrombin or with thrombin for exposure times of 1 and 2 min. At 6 min after at least 0.05 U/ml of thrombin, surface-bound aggregates were observed. The initial rate of adhesion increased with the amount of thrombin used for prestimulation. For adhesion to fibrinogen in the absence of prestimulation, platelet-derived ADP was a stimulator. Adhesion was shown to be independent of the ADP and arachidonic acid pathways in response to prestimulation with a low level of thrombin, 0.02 U/ml. For adhesion and cohesion, aggregation, in the presence of sufficient thrombin for prestimulation, 0.05 U/ml, ADP, serotonin and substances from arachidonic acid metabolism acted jointly to stimulate platelets.

Adenosine Diphosphate↗

Maximum fluid concentrations of materials released from platelets at a surface.

We examine the estimation of local concentrations of materials that are released from the dense and alpha-granules of platelets during accumulation of platelets upon collagen-coated glass. Platelet/red blood cell suspensions were perfused through a 1.3-mm-ID tube. Empirical data were used in a calculation procedure, based on diffusion and convection, designed to yield an upper bound on the interfacial fluid concentration (IFC) for each substance considered. The necessary empirical data are the rate of platelet accumulation and the maximum amount of material in the platelet capable of secretion. It was found that the IFC is dependent on the shear rate at the surface (G) and is proportional to G0.27. This means that an eightfold increase in flow rate would increase the IFCs approximately twofold. Serotonin, pyrophosphate, adenosine 5'-monophosphate (AMP), and adenosine 5'-triphosphate (ATP) were found not to be present in sufficient quantities to produce IFCs that could influence platelet aggregation if used alone at the IFC. A second set of materials, fibrinogen, fibronectin von Willebrand factor, and calcium, had IFCs less than their concentrations normally found in plasma. A third category, containing adenosine 5'-diphosphate (ADP) alone, had an IFC close to those known to affect platelet aggregation. The role of metabolites of arachidonic acid, which may promote or inhibit platelet aggregation, awaits further description.

Adenosine Diphosphate↗

Electrochemical surface shear rate evaluation in models of the renal artery.

Electrochemical measurements of surface shear rate were done in two renal artery models with 45 and 90-deg take-off angles to determine the extent to which the parent tube flow rate, flow division and branch shape influence flow at sites for atherogenesis. The dependence of surface shear rate on each of these independent variables was nonlinear; mathematical relationships which could predict surface shear rate at other flow rates, flow division ratios or vessel shapes did not emerge. The results of this work along with reports of others, which demonstrate great variability in location and extent of atherosclerotic lesions, support the conclusion that pathological studies and flow studies should be done simultaneously if the role of flow in atherogenesis is to be elucidated.

Arteriosclerosis↗

Platelet adhesion and release: interfacial concentration of released materials.

Platelet deposition on collagen-coated glass and release from adherent platelets were studied in tube flow. Shear rates between 80 and 320 s-1 were evaluated by use of washed porcine platelets radiolabeled with 51Cr and [3H]serotonin in Tyrode solution containing albumin, apyrase, and red blood cells. Cell accumulation was highest at the tube's inlet and was directly proportional to exposure time for all positions up to 20 cm from the entrance and for times up to 800 s. Release was lowest at the inlet, 60%, and increased to 90% downstream. The accumulation and release information served as input to a calculation that yielded ADP surface concentration values at the tube's surface. These ranged from 0.6 microM at 80 s-1 to 1.8 microM at 320 s-1. In a turbidimetric device, ADP concentrations of 0.5, 1.0, and 5.0 microM were required to induce shape change, 10 and 80% aggregation, respectively. Aggregation was also obtained with subthreshold ADP and collagen in combination. We surmise that platelet shape change could have occurred adjacent to the surface in preparation for adhesion, aggregation, and release at the surface, and that ADP and collagen acted synergistically.

Adenosine Diphosphate↗

Experimental evaluation of streamline patterns and separated flows in a series of branching vessels with implications for atherosclerosis and thrombosis.

Flow conditions in four models representing the aortic bifurcation, iliac bifuraction, and a renal artery branch were investigated at volumetric flow rates corresponding to Reynolds numbers from 1000 to 4000 over the complete range of flow division between daughter vessels. Qualitative flow streamline patterns and quantitative definition of those flow conditions leading to disturbed flow (flow separation ) were determined primarily at steady flow with a limited set of pulsatie experiments. Under conditions of no flow separation, common characteristic streamline patterns not parallel to the center lines of parent or daughter tubes were found for all models. These effects were accentuated with increasing Reynolds number. Flow separation was inducible through alteration of flow division between daughter vessels or by an increase in flow rate. Each of the four models had distinct combinations of flow division ratio and flow rate which gave: (1) no flow separation, (2) flow separation at the outside of the right daughter tube, and (3) flow separation at the outside of the left daughter tube. Models representing the renal artery also had regions of simultaneous left- and righthand separation on the outside of their daughter tubes. The separated flows observed here displayed streamlines forming an open vortex with flows entering and leaving. These regions, which occur only at distinct combinations of flow rate and flow division, may be key centers where platelet aggregates may form, release constituents, and cause vessel injury.

Aorta, Abdominal↗

Adhesion of platelets to artificial surfaces: effect of red cells.

Adhesion of platelets to several polymer- and protein-coated glass surfaces has been studied in vitro. The apparatus consists of a cylindrical probe rotating in a test tube containing the platelet medium and allows close control of fluid shear and mass transport. Suspensions of washed pig platelets constitute the basic platelet medium, and can be modified by adding back red cells and plasma proteins. Adhesion is measured via 51Cr-labeling of platelets. In the absence of red cells, identical low levels of adhesion were seen on all surfaces and saturation was reached within 2 min. In the presence of red cells, adhesion was greater. Saturation on all surfaces except fibrinogen and collagen again occurred within 2 min. The adhesion levels on polymer surfaces and glass were indistinguishable, while those on albumin were lower and those on fibrinogen were higher. Collagen was the most reactive surface. It did not equilibrate within 15 min., and kinetic data indicated a platelet diffusivity strongly dependent on hematocrit. These effects were attributed to rotational and translational motion of the red cells causing increased diffusion and surface-platelet collision energy.

Animals↗

Arterial bifurcation flows--effects of flow rate and area ratio.

Velocity profiles and surface shear rates, for three model symmetrical bifurcations made of glass from dimensions based on the arterial system, were investigated. The models studied had area ratios of 0.75, 1.02, and 1.29, with a common included angle of 75 degrees. Area ratio and parent tube flow rate were the two independent variables evaluated. Measurements were made with a tracer particle technique using cinephotography. Velocity profiles had their highest values on the inside, and lowest values on the outside, of the branch. Flow symmetry existed in the plane perpendicular to the plane of the bifurcation. Surface shear rates remained well above the daughter-tube developed values, between two and six diameters downstream from the carina. Shear rates below the daughter-tube developed value were found on the outside wall between the carina and two daughter-tube diameters downstream. Vortex-like flow was absent in this region for the 0.75 area ratio branch and was found above 900 Reynolds number in the 1.29 area ratio branch. The disturbed flow described by others in this region may not contain vortex-like streamlines for the physiologically important 0.75 area ratio.

Arteries↗