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This study presents the effects of red blood cell (RBC) hyperaggregation on the blood flow and pressure in the rat mesentery and cremaster network. We exclusively studied in situ non-vasodilated organs, in order to maintain the physiological regulation mechanisms. Dextran 500 was injected at different concentrations to increase RBC aggregation. The aggregation rate was measured on very small blood samples with an erythroaggregameter (SEFAM) which evaluated the disaggregating shear stress (tau D) needed to break the RBC aggregates. Microscopic observations and laser Doppler velocimetry were used to quantify the flow rate. The plasmatic dextran concentration (C) increase had different correlated effects: for example, tau D increased from 3 dynes cm-2 (for the control sample) to 14 dynes cm-2 (for C = 75 microM L-1); the flow rate was reduced threefold and very large aggregates were observed in the venules; the arteriolar pressure increased while venular pressure decreased. In order to differentiate the effects of RBC hyperaggregation from those of plasma hyperviscosity (due to dextran 500) on microcirculatory blood flow, we injected an RBC antiaggregating drug (troxerutine) (50 or 100 mg kg-1 i.v.). The consequences were a high reduction for (tau D) (from 14 dynes cm(-2)-9 dynes cm-2), smaller aggregates and higher blood flow in the venules. No effect of troxerutine was observed on plasma viscosity (plasma control: 1.9 cP with or without troxerutine; plasma with dextran at C = 75 microM L-1: 2.45 cP with or without troxerutine). The results strongly suggest that RBC aggregation has a significant influence on blood flow rate in the microcirculatory network.

Purpose: A strong embolic effect of iodized oil/drug mixtures injected in the hepatic artery appeared to be an efficient way of prolonging the contact time between drugs and tumor tissue. Therefore, the authors evaluated arterial and portal embolic effects after hepatic intra-arterial injection of iodized oils and various emulsions of iodized oil., Materials and Methods: Twenty-five pigs were monitored for the Doppler resistance index (DRI) in the hepatic artery and wedge hepatic vein pressure (WHVP) during 1 hour after injection of pure iodized oil, ultra-fluid or fluid, and four different emulsions of iodized oil ultra-fluid, into the hepatic artery., Results: Mean area under the curve (AUC) values of DRI increases varied from 20.3 to 24.2 after injection of pure iodized oils or water-in-oil emulsions, and were 13.2 for large-droplet oil-in-water emulsion and 8.2 for small-droplet oil-in-water emulsion. Mean AUC values of WHVP increases varied from 151.6 to 195.6 after injection of pure iodized oils or water-in-oil emulsions, and were 105.5 for large-droplet oil-in-water emulsion and 8.5 for small-droplet oil-in-water emulsion. There was a significant difference in DRI and WHVP modifications between small-droplet oil-in-water emulsions and all other products (P = .001), between the two oil-in-water emulsions and the two water-in-oil emulsions (P = .004), and between the two oil-in-water emulsions and pure iodized oils (P = .002)., Conclusion: After hepatic intra-arterial injection, water-in-oil emulsions and pure iodized oils provided a stronger embolic effect than oil-in-water emulsion, both in the hepatic artery and in the portal vein.

We compared blood viscosity and red blood cells (RBC) disaggregation shear stress in three mammalian species (humans, pigs and sheep) before and after adding water-soluble iodinated contrast media (CM): Ioxaglate (ionic CM) and Iopromide (non ionic CM). The two CMs had a diluting effect on the blood of the three species, which resulted in a viscosity decrease at all shear rates. However, viscosity rose slightly at low shear rates (in relation to increase of RBC aggregation) and low CM concentrations (10%), regardless of the ionic or non ionic nature of the CM. The two CMs had a similar proaggregant effect in human and pig's bloods. The proaggregant effect was slightly more pronounced with the ionic CM. We concluded that the pig is more suitable than the sheep for in vivo assessment of blood/CM mixture.

Purpose: To optimize use of iodized oil for diagnostic computed tomography (CT) enhanced with iodized oil and for interstitial radiation therapy with iodine-131-labeled iodized oil, the authors quantified the distribution of iodized oil after injection of different formulations of iodized oil into the hepatic artery., Materials and Methods: I-125-labeled iodinated ethyl ester of poppyseed oil in two viscosities (iodized oil ultrafluid [viscosity, 0.04 Pa/sec] and iodized oil fluid [viscosity, 0.17 Pa/sec]) was injected (pure forms and three different emulsions of each) into the hepatic artery of rabbits bearing VX2 tumors in the liver. All rabbits received a radiation dose of 4 MBq per kilogram of body weight in 0.1 mL/kg iodized oil. Animals were killed 4 days later, and iodized oil uptake was evaluated in the tumor, nontumorous liver, and lung., Results: There were no statistically significant differences in uptake between pure iodized oil ultrafluid or fluid or between the same type of emulsions made with each type of iodized oil. Lung uptake was significantly higher with pure iodized oil ultrafluid and fluid (19.75 kBq/g +/- 3.25 [standard error of the mean] vs 19.48 kBq/g +/- 6.15, respectively) than with any emulsions (range, 3.72-8.14 kBq/g; mean, 5.68 kBq/g) except the small-droplet oil-in-water emulsion (10.51 kBq/g +/- 1.18). The ratio of tumor to nontumorous liver uptake of iodized oil was significantly higher with large-droplet water-in-oil emulsions made of iodized oil ultrafluid or fluid (10.26 +/- 2.88 and 9.53 +/- 0.64, respectively) than with any other product (range, 4.07-5.38; mean, 4.49)., Conclusion: Use of large-droplet water-in-oil emulsions limited lung uptake and increased tumor uptake of iodized oil after intraarterial hepatic injection in rabbits bearing VX2 tumors in the liver.

We describe the preparation of a lyophilized material containing purified human pancreatic alpha-amylase and the certification of its catalytic concentration. The enzyme was purified from human pancreas by ammonium sulphate precipitation and chromatography successively on DEAE-Sephacel, CM-Sepharose and Sephadex G-75. The purified enzyme had a specific activity of 52.9 kU/g protein and was > 99% pure on polyacrylamide gel electrophoresis. Only trace amounts of lipase and lactate dehydrogenase were detected in the purified fraction. The purified pancreatic alpha-amylase had a molar mass of 57,500 g/mol and an isoelectric point at 7.1. The material was prepared by diluting the purified alpha-amylase in a matrix containing PIPES buffer 25 mmol/l, pH 7.0, sodium chloride 50 mmol/l, calcium chloride 1.5 mmol/l, EDTA 0.5 mmol/l and human serum albumin 30 g/l, dispensing in ampoules and freeze-drying. The ampoules were homogeneous and the yearly loss of activity on the basis of accelerated degradation studies was less than 0.01% at -20 degrees C. The certified value for alpha-amylase catalytic concentration in the reconstituted reference material is 555 U/l +/- 11 U/l when measured by the specified method at 37 degrees C. The material can be used to verify the comparability of results from laboratories, for intra-laboratory quality control or for calibration of alpha-amylase catalytic concentration measurements.

Purpose: To evaluate circulatory alterations induced by intra-arterial injection of iodized oil and emulsions of iodized oil with an anticancer drug., Materials and Methods: The viscosities and stability were evaluated in arterial flow of iodized oil and the emulsions. Doppler ultrasound was used to quantify the embolic effect in the arteries of rabbits. The behavior of doxorubicin and iodized oil in the rat cremaster muscle was studied with videomicroscopy., Results: The emulsions did not break up after injection, and the size of discontinuous-phase droplets did not change. The embolic effect did not correlate with viscosity. The thinnest water-in-oil emulsion had the lowest embolic effect and induced homogeneous distribution of iodized oil droplets in the arterial tree., Conclusion: Changes in the formulation of emulsions obtained with the same proportions of drug and iodized oil change the distribution of iodized oil in the arterial tree, the location at which the drug is released, and the embolic effect.

Optic disc blood flow velocity was measured in healthy patients, those with primary open angle glaucoma (POAG), and patients with normal pressure glaucoma (NPG). The velocity of the red blood cells (RBCs) in the capillaries of the optic nerve head (ONH) has been measured with a laser Doppler velocimeter (LDV), and blood viscosity has been evaluated notably by determining the aggregability of the RBCs with an erythroaggregameter. Our results in POAG patients and NPG patients showed that their optic nerve blood flow velocity was reduced and that the aggregability of the RBCs was increased. The hyperaggregability of the erythrocytes is responsible for the increase of the local viscosity in the papillary capillary network. These haemodynamic modifications observed in patients with glaucoma support the hypothesis of a vasogenic mechanism that could impair the optic nerve in glaucoma patients.

In order to evaluate the optic nerve head perfusion in patients with primary open-angle glaucoma (POAG), we measured the velocity of the red blood cells (RBCs) in the capillaries of the optic nerve head with a laser-Doppler velocimeter and evaluated the blood viscosity by determining the capacity of the RBCs to disaggregate with an erythroaggregameter. Our results showed that in POAG patients optic nerve blood velocity was reduced and that the aggregability of the RBCs was increased. The two parameters were not significantly correlated, possibly because of local papillary autoregulation and anatomical variability in the papilla vessels. These two factors could explain why the same rheological anomaly in two subjects could lead to different responses in blood velocity. The RBC hyperaggregability cannot be explained by quantitative modifications of the plasma proteins. Modifications in the membrane of the RBCs could indeed be responsible for hyperaggregability, since our data suggest that deformability of the RBCs is impaired in glaucoma.

The Dibie-Musset (DM) vena caval filter was evaluated on a hydraulic test bench reproducing flow conditions in the inferior vena cava: pressure, flow, viscosity, diameter and elasticity of the conduit. The results were compared with those obtained with the Greenfield filter (GF). In addition to classical measurements (captation and loss of load) we measured the velocity profile with a Doppler ultrasonic probe proximal and distal to the filter to study flow conditions before and after embolisation of clots. In order to circumvent the difficulties encountered with the use of real thrombi, chemical gels with visco-elastic properties, evaluated by viscosimetry, similar to those of blood clots, were used. Clots 45 mm long and 4 mm diameter were injected in several series of measurements. The DM filter was stable and did not migrate. In the horizontal position (flexible conduit) the DM filter was significantly more effective than the GF for less than 5 clots injected successively. The filtration capacity of both filters decreased with the number of clots captured. In the vertical position (rigid conduit), when there are less than 5 clots injected the two devices were perfectly effective. There was no significant difference between the two filters when 10 clots were injected. The loss of load resulting from the presence of the filter and clots was greater with the DM filter because of the greater captation capacity. However, the velocity profile distal to the filter was less disturbed with the DM filter because there was a more uniform distribution of the clots captured over the surface of the filter.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the effects of moderate changes in red blood cell RBC aggregation on blood flow in the vasodilated vascular bed of an isolated rat heart. We compared a non-aggregating RBC suspension (in Krebs-albumin medium) with RBC suspensions in 1% and 2% Dextran 70 (MW 70000), exhibiting two different degrees of moderate aggregation. Degrees of aggregation were precisely estimated by in vitro laser aggregometry. Each heart was perfused by the non-aggregating RBC suspension and by one aggregating RBC suspensions. Blood flow was measured in a range of perfusion pressure from 40 to 80 mm Hg. For the three RBC suspensions, linear pressure/flow relationships were found. From the comparison between the pressure/flow relationships obtained with Krebs albumin medium and either 1% or 2% Dextran, it was possible to compare in vivo the contribution of RBC to the viscosity (i.e., the relative apparent viscosity) in the 2 aggregating RBC suspensions with that of the non-aggregating RBC suspension. The contribution of RBC to the viscosity was found to be 20% to 25% lower in the 1% RBC suspension than in the non-aggregating RBC suspension. With 2% Dextran which induced a higher degree of aggregation no differences were found between the relative apparent viscosities of the aggregating and the non-aggregating suspension. From the comparison between RBC in 1% Dextran and Krebs-albumin, we concluded that in vivo a moderate RBC aggregation reduces viscous resistance due to the presence of blood in a vascular network. Since no more effect of RBC aggregation per se was found when the degree of aggregation was higher (with RBC in 2% Dextran), this suggests that, in this case, aggregation induces opposite effects along the myocardial vascular network which cancel each other out, thus inducing a nil net balance.

The vascular participation to the optic nerve pathogenesis has been contradicted. The red blood cell velocity in the optic nerve capillary with a laser Doppler velocimeter, an atraumatic and reliable method, and the aggregability was determined with an erythroaggregameter to know whether an erythrocyte hyperaggregability could slow down the optic nerve blood flow as it has been previously demonstrated in an experimental study. The experiment on the open angle glaucoma patients showed that their optic nerve blood flow was reduced, and their erythrocyte aggregability significantly increased. The two parameters were not significantly correlated, certainly because of a local papillary autoregulation and of the papilla vessels variability, those two factors could modulate the blood flow response to blood qualitative changes. The erythrocyte hyperaggregability could be explained by erythrocyte membrane modifications that could agree with the glaucoma heredity.

We study capillary microcirculation on the optic nerve head and its interrelation with blood rheological modifications. The mean maximal velocity has been evaluated in the capillaries of the rabbit optic nerve with a laser doppler velocimeter, in physiological conditions and after intravenous Dextrane 250 injections. Dextrane 250 increases red blood cells aggregation and induces blood hyperviscosity at low flow rates. This hyperaggregation is determined with a reflectometric method. Experimental results show a significant reduction of blood velocity when blood viscosity increases. In our present study, we compare blood capillaries flow rate in the optic nerve, between two groups: healthy humans and subjects suffering from glaucoma. The aggregation level is simultaneously measured for the two groups. First results seem to prove that blood flow rate decrease is associated with red blood cells aggregation increase for the second group.

A Laser Doppler velocimeter (LDV) was modified in order to reduce the dimensions of the crossing section of the two light beams. This LDV has been used on plane capillary tubes (100 mu m less than or equal to inside thickness less than or equal to 400 mu m) in which different sorts of suspensions were flowing. The flow rate Q, and pressure, delta p, measurements were recorded simultaneously. The velocity profile measurements were done. We have verified that the velocity profile blunting depended on hematocrit, flow rate. Such profiles were in good agreement with theoretical ones obtained with a model where aggregation and deformation levels were described by characteristic coefficients involved in a viscosity equation.

The measurements of erythrocyte orientation, obtained through a spin labeling technique, are compared with a phenomenological model. Several rheological conditions are varied: hematocrit, suspending medium viscosity, blood age, artificial reversible aggregation. We found that the onset of orientation is very sensitive to any variation of these conditions, and that its measurement would be a good method to assess erythrocyte deformability. A critical shear rate for the orientation process is then determined and compared to the corresponding parameter obtained from viscosity measurements of identical suspensions. A close qualitative relationship is found between the two sets of values of the critical shear rate.

Erythrocyte sedimentation of normal and pathological human bloods at varying controlled shear rates has been measured. Erythrocyte sedimentation rate (ESR) was found to reach a maximum at a characteristic shear rate gamma c [gamma c less than .1 s-1 for normal bloods; gamma c greater than .1 s-1 for pathological bloods]. Records of viscosity versus shear rate exhibit a break near gamma c. Examples show that ESR is well correlated with viscometric data.

An optical method is proposed for studying rouleaux formation and red blood cells (RBC) orientation. Both relations, first between m, the mean number of RBCs per rouleau and reflectivity, and second between the oriented RBCs fraction and the variation of the isotropic reflectivity are proposed. Our experimental data about aggregation relaxation time and orientation relaxation time are discussed and compared to viscometric results.

The viscosity of normal and pathological blood samples is determined using a Couette viscometer (5.10-2s-1 less than or equal to shear rate less than to equal to 125 s-1). In different pathological cases, the rheograms show an abnormal behaviour. The viscosity curves exhibits a break between 0.1 and 1 s-1. This work shows the results obtained in the case of a patient suffering from Raynaud's disease. During therapy with lysine acetylsalycilate one observed the gradual shift of the breack to low shaer values, then, the return to a normal rheogram. In the same time, acroyanosis has completely disappeared, recovering normal nail growth.

We propose a constant cephalic blood perfusion method especially suitable to the rat. Cerebrovascular blood pressure is artificially regulated by an extracorporeal circuit with a perfusion pump and a Starling valve. A hemorrheological evaluation allows one to demonstrate an extracorporeal circuit that shows a growing pathological evolution, which can be purposely accelerated by iterative ischemic episodes. This method can be used (as shown by some examples) as a model for cerebrovascular failure or to study deleterious effects of the extracorporeal circuit.