Hemorheology in asymptomatic HIV-infected patients.

Although cardiac and vascular complications have been recognized among patients infected with the Human Immunodeficiency Virus-1 (HIV-1), their vascular biology and rheology have not been studied. Rheology of red blood cells (RBC) was assessed with an erythroaggregometer in 22 HIV-1 infected asymptomatic patients (pts) and 17 healthy HIV negative controls (C). All participants were normotensive, nondiabetics, had normal lipid levels and had an hematocrit ranging from 37 to 44% and hemoglobin levels > or = 12 g/100 ml. Patients had a shorter RBC aggregation characteristic time than controls (1.49 +/- 0.17 vs. 2.04 +/- 0.41 s, p = 0.001) and an increased disaggregation shear rate (166 +/- 34.9 vs. 122 +/- 25.4 s(-1), p = 0.001). This hyperaggregation tendancy was associated with increased gamma-globulin (18.3 +/- 3.3 vs. 13.7 +/- 1.9 g/l, p = 0.01) and fibrinogen (3.52 +/- 0.57 vs 3.03 +/- 0.48 g/l, p = 0.003) levels and with an increased erythrocyte sedimentation rate (ESR) (25 +/- 14.3 vs. 12.3 +/- 7.5 mm, p = 0.02). Even in patients with ESRs ranging within normal values (< or = 20 mm), the aggregation characteristic time was found lower in patients than in controls (p = 0.004). There was no correlation between these rheological changes and the CD4+ T-cell count. The 17 patients receiving an antiviral therapy had lower CD4+ T-cell counts than their 5 untreated counterparts (244.7 +/- 167 vs. 410 +/- 106/mm3, p = 0.025), and a higher disaggregation shear rate (177.4 +/- 38.2 vs. 127 +/- 25.4, p = 0.01). Thus, an impairment of rheological characteristics is observed in asymptomatic HIV-I infected patients in association with changes in plasma proteins.

Reduced reactive hyperemia in HIV-infected patients.

BACKGROUND: Given that several pathology-based studies reported some degree of coronary and arterial vasculopathy in HIV-infected patients, we investigated whether abnormal vascular reactivity may also be found in these patients. METHODS: Vascular reactivity was assessed noninvasively using finger-skin blood-flow monitoring by laser-Doppler flow measurement in 10 HIV-infected-patients (mean CD4 T-cell count, 350+/-84 cells/mm3) with cardiac symptoms (previous myocardial infarction or left-ventricular dysfunction) and/or HIV-related protease inhibitor-induced hyperlipemia (group 1, symptomatic), 19 HIV-infected patients free of cardiac disease, hyperlipemia, and previous opportunistic infections (mean CD4 T-cell count, 333+/-175 cells/mm3; group 2, asymptomatic), and 19 healthy control subjects (group 3). Laser-Doppler flow was measured at baseline, during postocclusive hyperemic response following transient interruption of brachial blood flow (reactive hyperemia), during transcutaneous delivery of acetylcholine (Ach) using iontophoresis (endothelium-dependent dilation) and after sublingual nitroglycerin administration (endothelium-independent dilation). RESULTS: During reactive hyperemia, the absolute increase in flow was found to be lower in asymptomatic HIV-infected patients than in controls (median values [25th-75th percentile]: asymptomatic: 300 [200-400]; versus controls: 600 [400-750] arbitrary units [AU]; p< or =.0001). This abnormality was more pronounced in symptomatic patients (100 [100-200]; p< or =.0001). There was also a reduced peak/baseline flow ratio (symptomatic: 1.14 [1.1-1.2]; asymptomatic: 1.40 [1.25-1.5]; versus controls: 1.83 [1.6-2.2]; p<.0001 for both comparisons) and a reduced hyperemic response, as assessed by the curve of area under the flow versus time from deflation to the end of the hyperemic response (symptomatic: 1850 [1100-2225]; asymptomatic: 6000 [2850-7950]; versus controls: 23,735 [16,000-31, 800] AU x sec; p<.0001 for both comparisons). Although there was no statistically significant difference in acetylcholine (Ach)-induced increases in flow between asymptomatic HIV patients and controls (peak/baseline flow ratio: 6 [4.4-10] versus 5.3 [4-8]; p =.47), a trend to lower values was seen in symptomatic patients (4.4 [1.2-5]; p =.06). Administration of 0.4 mg sublingual nitroglycerin resulted in increases in flow without statistically significant difference between patients and controls: peak/baseline flow ratio for symptomatic: 2.4 [1.9-2.7]; asymptomatic: 2.1 [1.75-2.34] versus controls: 1.97 [1.8-2.4]; p =.2 and.83, respectively). CONCLUSIONS: Postischemic reactive hyperemia is reduced in HIV-infected patients. In addition, there was is trend for a reduced response to Ach only in those with cardiac disease and/or hyperlipemia.

Thrombosis of angiographic catheters in humans: experimental study.

One of the major problems in the use of catheters is their thrombogenicity since the embolization of clots near the central nervous system or the coronary arteries can cause permanent damage. Catheter thrombogenicity was evaluated in humans during angiographic procedures by their tendency to become occluded. Characterization of catheters was achieved using roughness measurements, FTIR with ATR, DSC and ESCA. The catheters were 5 commercially available catheters, made mainly of polyethylene, Pebax or polyamide sterilized and ready for clinical use. Thirty-one patients due to have an angiographic procedure and with normal blood and hemodynamic parameters were included in the study. The 50 cm catheter test sample was inserted through an introducer into the femoral artery at the beginning of an angiographic procedure. The outcoming blood flow rate (BFR) was continuously monitored by a special computerized device for 15 min or until the total amount of blood reached 30 ml. The angiographic procedure was then normally resumed. DSC and FTIR showed results consistent with the expected composition of catheters. ESCA results showed very high Si/C ratios and could not be explained in all instances. Occlusion of the catheters occurred in 44% of the cases and the average time to obtain occlusion was 8.5 min (3-15 min). Values of the decrease rate of BFR in ml/min2 allowed separation of the catheters into 3 groups of low, medium and high thrombogenicity. However, occlusion occurred at least one time for each type of catheter. Blood volume and BFR curves vs. time allowed the determination of 3 main types of thrombotic behavior: type I shows no significant reduction of BFR; type II shows a progressive decrease in flow rate; type III is much less frequent and shows an abrupt decrease of BFR either quickly followed by a compensatory increase and resuming of a steady flow or by abrupt occlusion. In type II curves the pattern of occlusion follows a classical diffusion model because the Peclet number is greater than 1 and then the classical Higbie solution for diffusion could be used. The most thrombogenic material was the smoothest. There was no correlation between surface chemical composition and thrombogenicity. However, catheters that were based on PE appeared less thrombogenic than PA catheters in this study.

Effects of contrast media on blood rheology: comparison in humans, pigs, and sheep.

PURPOSE: To compare whole blood viscosity and erythrocyte aggregation in humans, pigs, and sheep, before and after adding water-soluble iodinated contrast medium (CM). METHODS: Two CMs were studied: iopromide (nonionic) and ioxaglate (ionic). The blood-CM viscosity was measured with a Couette viscometer. Erythrocyte aggregation was measured with an erythroaggregometer. RESULTS: The blood-CM viscosity was increased up to +20% (relative to pure blood) with a CM concentration of 0%-10%. At CM concentrations from 10% to 50%, the viscosity decreased. The disaggregation shear stress was increased (relative to pure blood) at low CM concentration (0%-10%). When the CM concentration increased from 10% to 20%, the disaggregation shear stress was decreased, except with the pig blood-ioxaglate mixture. CONCLUSION: At low CM concentration the blood viscosity was increased in pig, sheep, and humans and the disaggregation shear stress was increased in pig and humans. The aggregation of sheep blood was too low to be detected by the erythroaggregometer. This rise can be explained by the formation of poorly deformable echinocytes. At higher CM concentration, the viscosity and the disaggregation shear stress decreased in relation to the blood dilution. We conclude that pig blood and sheep blood can both be used to study the effect of CM injection on blood viscosity. Nevertheless, the rheologic behavior of pig blood in terms of erythrocyte aggregation is closer to that of human blood than is sheep blood when mixed with CM. Pigs could thus be more suitable than sheep for in vivo studies of CM miscibility with blood during selective cannulation procedures.

Effects of red blood cell hyperaggregation on the rat microcirculation blood flow.

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.

Modification of arterial and portal hemodynamics after injection of iodized oils and different emulsions of iodized oils in the hepatic artery: an experimental study.

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.

Theoretical and experimental study of intermittent blood flows in microcirculation: application to the in-vivo determination of compliance.

A new theoretical approach was used to study the nonlinear response of a microvascular segment subjected to a pressure step at one end. The method is suitable for both large and small deformations of the vessel wall in the case of an elastic response of the segment. It is shown that the use of this simulation permits an indirect determination of the compliance of the vessel. The procedure is applied in two cases of major interest: first the in-vivo study of the intermittent blood flow in the microcirculation, and second, the analysis of experiments using micropipettes. The resulting values of the compliance agree with other values found in the previous studies. The theoretical method is particularly adapted to nonlinear equations.

Comparative viscosity and erythrocytes disaggregation shear stress of blood-radiographic contrast media mixtures in three mammalian species.

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.

Quantification of tumor uptake of iodized oils and emulsions of iodized oils: experimental study.

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.

Production and certification of an enzyme reference material for pancreatic alpha-amylase (CRM 476).

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.

Circulatory alterations induced by intra-arterial injection of iodized oil and emulsions of iodized oil and doxorubicin: experimental study.

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 nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma.

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.

Blood flow rate in the microvasculature of the optic nerve head in primary open angle glaucoma. A new approach.

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.

[In vitro evaluation of Dibie-Musset vena caval filter]. / Evaluation in vitro du filtre cave Dibie-Musset.

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)

Red blood cell aggregation and blood viscosity in an isolated heart preparation.

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.

[Hemo-rheology of glaucomatous neuropathy]. / Hémorhéologie de la neuropathie glaucomateuse.

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.

[Laser-Doppler velocimetry on the optic nerve head and hemorheology. Animal experiments. First results in humans]. / Vélocimétrie laser-Doppler sur la tête du nerf optique et hémorhéologie. Expérimentation animale. Premiers résultats chez l'homme.

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.

Extracorporeal cephalic blood autoperfusion method in the rat. Hemorrheological evaluation and proposed pharmacological uses.

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.