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Biomedical subjects

M Y Jaffrin

Publications and source records attributed to M Y Jaffrin.

At least 19 recordsLinked to original sources

Plasma fractionation by dead-end membrane filtration: effects of membrane properties and plasma flux.

Plasma fractionation by membrane filtration permits the reinfusion of the patient with his own albumin. In this study, the influence of membrane nature and plasma flux on plasma fractionation in dead-end mode is investigated with acetate hollow fiber filters. It is found that transmembrane pressure TMP rises exponentially with time, the rate of increase being proportional to plasma flux. The faster TMP rises, the faster the drop in sieving coefficient SC. It is also found that albumin SC is a function of TMP and not of plasma flux. Theoretical analysis of the dead-end filtration was performed. This theoretical model indicates that the observed variation of TMP with time is consistent with the assumptions that pore volume decreases proportionally to the filtrate plasma volume.

Blood Component Removal

Dynamic filtration of blood: a new concept for enhancing plasma filtration.

We have shown previously that blood flow pulsations created by intermittent squeezing of the inlet blood line significantly increased the plasma filtration rate in membrane plasmapheresis. However, in order to avoid hemolysis, the filtration increase had to be limited to about 50%. We have now devised a more efficient pulsation generator. By properly matching the tubing compliance and the pulsation amplitude, it is possible to extract 50 ml/min of plasma from 90 ml/min of blood at 36% hematocrit with a 1000 cm2 polypropylene hollow fiber filter without hemolysis. Simultaneous recording of the time course of plasma filtration rate measured by an electromagnetic flow meter and transmembrane showed that the increase in mean plasma flow rate was due to a dynamic filtration process which prevents the establishment of concentration polarization. The transmembrane pressure (Ptm) increases over a 0.5-second interval when the tube is squeezed. The membrane responds with an increase in filtration since the concentration polarization layer takes a few seconds to build up. The Ptm then drops when the tube is released before the polarization layer has time to build up appreciably and a sudden acceleration of the blood flow (velocity spike) helps clean the membrane, reducing the polarization. Tests with bovine show that the system is very efficient in reducing membrane plugging with small area filters.

Animals

Comparison of polyamide and polypropylene membranes for plasma separation.

Plasma separation experiments were made with polyamide experimental prototype hollow-fiber plasma filters with surface areas between 0.025 m2 and 0.1090 m2 using bovine blood collected in acid citrate dextrose (ACD). The maximum filtration velocity rose with the wall shear rate gamma w as gamma w 0.72 +/- 0.02 and decreased with the length of fiber L as L-0.41 with a correlation coefficient of 0.97 +/- 0.02. The results were similar to those with polypropylene fibers. We also investigated the occurrence of hemolysis as a function of shear rate and transmembrane pressure. The free hemoglobin concentration of filtered plasma was checked using a U.V. spectrophotometer. It was concluded that polyamide membrane filters can be safely used for plasma separation from blood.

Animals

Albumin recovery enhancement in membrane plasma fractionation using pulsatile flow.

In therapeutic plasmapheresis using cascade filtration, it is important to maximize albumin recovery while rejecting as many gamma-globulins as possible. Several membrane fractionation techniques were investigated using fresh bovine and human plasma and cellulose acetate filters (PF 100, AKZO). In dead end mode the sieving coefficients were found to decrease as transmembrane pressure increased. This was due to membrane plugging during the course of filtration after about 20 minutes which lead to a rapid increase in transmembrane pressure. In single pass mode the albumin recovery factor generally remains around 40% since the permeate flux is much less than the inlet flow. When strong pulsations (4 to 6 Hz) were superposed on the inlet plasma flow in single pass mode, the albumin sieving coefficient remained at about 0.95 while the permeate flux was increased by 106%. As a result a recovery factor of more than 80% could be sustained for at least 90 minutes without membrane plugging. Therefore pulsatile flow plasma fractionation seems to be an interesting approach to combine continuous operation with high albumin recovery.

Animals

Simultaneous convective and diffusive mass transfers in a hemodialyser.

The mass transfer in a hemodialyser in the presence of combined dialysis and ultrafiltration has been calculated by integration of mass fluxes across the boundary layers in blood and dialysate phase taking into account the partial rejection of solute as well as changes in local blood flow and ultrafiltration flux along the membrane. Clearances of creatinin, vitamin B12, and myoglobin have been calculated as a function of blood and ultrafiltrate flow rate and were found to be in good agreement with in vitro measurements. The data suggest the following empirical correlation for the hemodiafiltration clearance.

Models, Theoretical

Plasma filtration in Couette flow membrane devices.

This report investigates the effects of transmembrane pressure (ptm), rotation speed, and membrane characteristics on the performance of a rotating membrane device for separating plasma from whole blood. This device consists of 58 cm2 polymeric membrane rotating at high speed (3,000-4,000 r/min) inside a concentric cylinder and produces a Couette type flow in a gap 0.9 mm thick. Blood enters tangentially at the top, exits tangentially at bottom, and plasma is collected by an axial duct. It is found that this device yields maximum filtration velocities (plasma filtration flux per unit area) in the range of 0.5-0.8 cm/min, which are 10-20 times larger than those obtained by using hollow fiber plasma filters. This high performance is not due to the effect of centrifugal forces on red blood cells but rather to the very high shear rates, on the order of 20,000 sec-1, generated in the gap by toroidal flow instabilities (Taylor vortices). When a 0.8 micron pore size Nuclepore (polycarbonate) membrane is used, the filtration velocity presents a narrow peak of 0.6 cm/min at ptm = 10 mm Hg at 3,000 r/min and decreases to 0.35 cm/min at larger ptm. With a 0.5-micron pore nylon membrane the filtration speed increases continuously with ptm and reaches a plateau of 0.5 cm/min.

Cell Separation

High shear rate hemofiltration: influence of fiber dimensions and shear rates.

The variation of ultrafiltration flow rate (QF) at high transmembrane pressure with inlet wall shear rate (gamma w) was found to be proportional to gamma wn, with n ranging from 0.45 to 0.55, when gamma w increases up to 4,500 s-1. To test whether long filters operated at high shear rates were more efficient than shorter ones for the same inlet blood flow, we made experiments with 10- and 20-cm filters with same number of fibers (550) at various shear rates from 700 to 3,000 s-1. The filtration rates provided by the 20-cm filter were found to be 5-15% larger than those provided by two 10-cm filters arranged in parallel and 10-20% smaller than those provided by two 10-cm filters arranged in a series. The explanation lies in the rapid decay of QF with distance from the inlet due to the developing concentration boundary layer. When pulsations are imposed on the inlet blood flow, the filtration rate was seen to increase by 10-20%, and the effect of plugging was seen to decrease in small-area hemofilters.

Animals

In vitro evaluation of a bioartificial pancreas under various hemodynamic conditions.

A bioartificial pancreas in which isolated islets of Langerhans are placed between two polyacrylonitrile membranes, blood circulating successively above the upper and below the lower membranes following a U-shaped circuit, has been developed. The two parts are connected by an outer loop consisting of a thin tubing. The length of this tubing determines the magnitude of the flow rate of blood through the device. The aim of this work was to determine experimentally the optimal configuration of the system containing isolated rat islets and a Krebs buffer circulating through the device. The amount of insulin released by the bioartificial pancreas was determined during a 20-mM square-wave glucose stimulation. First, the inlet pressure was set at 100 mm Hg, and the effect of the length of the tubing was investigated with two devices perfused simultaneously. For a short tubing (flow rate, 20 ml/min), a sharp increase in insulin release in response to glucose was observed; it increased within 4 min from 217 +/- 50 to 761 +/- 237 microU/500 islets/min (p less than 0.05), the peak value being reached at 11 +/- 2 min following the beginning of the stimulation. For a long tubing (flow rate, 3 ml/min), the increase in insulin release was more sluggish. It increased from 133 +/- 53 to 222 +/- 43 microU/500 islets/min at 4 min, the peak value being reached only at 20 +/- 3 min. These data are consistent with a more efficient diffusional transfer of insulin in the case of the high circulating flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins

Modelling of plasma-separation through microporous membranes.

Available mathematical models of ultrafiltration have been used to predict changes in maximum plasma filtration rate with wall shear rate for given filters and blood properties. We have done many plasmapheresis experiments in vitro, using hollow-fiber filters (500-1000 cm2) and fresh bovine blood collected on ACD or heparin. The comparison between predicted and experimentally obtained filtration rates was good for models based on the concentration polarization theory and lift velocity theory. In other experiments with pulsatile inlet flow we found that plasma filtration rate increased by 20 to 50% compared to non-pulsatile conditions. These results are in good agreement with the modified model of ultrafiltration incorporating pulsating flow. This paper presents relationships between plasma filtration velocity (steady and pulsating flow) and hemolysis limit as a function of wall shear rate and filter size.

Blood Flow Velocity

Analysis of ultrafiltration and mass transfer in a bioartificial pancreas.

A bioartificial pancreas is an implantable device which contains insulin secreting cells (Langerhans islets), separated from the circulating blood by a semi-permeable membrane to avoid rejection. This paper describes the operation of such a device and evaluates the respective contributions of diffusion and ultrafiltration to the glucose and insulin mass transfer. It is shown that the pressure drop along the blood channel produces across the first half of the channel an ultrafiltration flux toward the islet compartment followed in the second half by an equal flux in reverse direction from islets to blood. The mass transfer analysis is carried out for an optimal geometry in which a U-shaped blood channel surrounds closely a very thin islet compartment formed by a folded flat membrane. A complete model of insulin release by this device is developed and is compared with in vitro data obtained with rats islets. Satisfactory kinetics is achieved with a polyacrylonitrile membrane used in hemodialysis. But the model shows that the membrane hydraulic permeability should be increased by a factor of 10 to significantly improve the performance.

Acrylic Resins

A model of ultrafiltration and glucose mass transfer kinetics in peritoneal dialysis.

We have investigated the variation with dwell time of dialysate volume and glucose concentration during continuous ambulatory peritoneal dialysis using a one-pool model. No assumption was made regarding the ultrafiltration rate that was calculated by the model. Results show that the volume ultrafiltered during dwell time is an increasing function of peritoneal membrane hydraulic permeability and a decreasing function of glucose mass transfer coefficient (MTC). For large MTC and low initial glucose concentration there is reabsorption of dialysate into the blood at large dwell times. For a 6 h dwell time, glycerol (92 daltons) is a more effective osmotic agent than glucose (198 daltons) at the same weight concentration. These results are in quantitative agreement with published clinical studies.

Biological Transport, Active

Membrane plasma separation through small-area, hollow-fiber filters.

The filtration capabilities of small polypropylene hollow-fiber plasma filters with membrane areas ranging from 100 to 1,000 cm2 have been investigated. It is found that the filtration flux per unit membrane area is approximately proportional to the wall shear rate gamma w at least up to gamma w = 7,500 s-1. As a result, the total filtration flow rate increases very little when the number of fibers is increased as the increase in membrane area is offset by the decrease in shear rate, but it increases with the fiber length L as L 2/3. Hemolysis occurs when the transmembrane pressure exceeds a certain threshold, but this threshold is itself an increasing function of shear rate. As a result, it is possible to circulate high blood flow rates even in very small filters (100 cm2) without hemolysis, provided the fiber length is below a critical value.

Animals

Aortic input impedance in heart failure: comparison with normal subjects and its changes during vasodilator therapy.

This study was aimed at the evaluation of aortic impedance in patients with congestive heart failure. Aortic impedance (simultaneous measurements of aortic pressure and blood flow), mean (Wm) and pulsatile (Wp) powers were compared in 11 normal subjects and in 12 patients with heart failure. Pulse wave velocity (C: modified Moëns-Korteweg equation, simultaneous measurements of aortic pressure and radius) was determined under control conditions in all normal subjects and in 7 patients with heart failure. Impedance curves in patients with heart failure were characterized by increased values of the impedance modulus at 0 Hz (peripheral resistance) and at low frequencies. The characteristic impedance, C, and phase were not different from normal subjects. In six patients with heart failure, impedance curves were studied during nitroprusside infusion. During the infusion of the vasodilator, the impedance modulus at 0 Hz and at low frequencies decreased. The characteristic impedance was unchanged. The zero intercept of the phase was shifted towards lower frequencies. These results show that the changes in impedance curves in patients with heart failure are due to greater peripheral resistance and wave reflection. During nitroprusside infusion the stroke volume increased and the aortic blood flow became more pulsatile (greater values of low frequency components). This modification accounts for the increased values of Wm and Wp, and is related to decreased peripheral resistance and wave reflection.

Adult

A U-shaped bioartificial pancreas with rapid glucose-insulin kinetics. In vitro evaluation and kinetic modelling.

The lag in insulin release in response to glucose is an obstacle to the development of hybrid pancreatic devices, in which an artificial membrane protects transplanted islets against immune rejection. We designed a U-shaped bioartificial pancreas, in which the blood channel surrounds the islet chamber consisting of two flat membranes; blood circulates successively above the first membrane and then in the reverse direction, below the second membrane. Isolated rat islets were introduced into the chamber, which was perfused with Krebs buffer, and the kinetics of insulin release in response to glucose was determined. During a 20-min, 2.8-20-mM, square-wave glucose stimulation, insulin release in the effluent of the device rose from 0.7 +/- 0.2 to 3.2 +/- 1.0 ng/100 islets/min (P less than 0.05) within 3 min, and reached a maximal level of 12.8 +/- 3.3 ng/100 islets/min at 10 min; 5 min after the return of the glucose concentration to substimulatory level, insulin release dropped from 11.3 +/- 1.5 to 8.0 +/- 1.7 ng/100 islets/min (P less than 0.05), and reached basal value (1.0 +/- 0.2 ng/100 islets/min) 40 min after the end of the stimulation. A 0.1-mM/L/min ramp increase in glucose concentration triggered a significant rise in insulin release (P less than 0.02) when the glucose concentration reached 5.3 +/- 0.2 mM; islets concomitantly perifused within a chamber set up without membrane responded to the same glucose stimulation 5 min earlier. For up to 1000 islets, insulin release in response to glucose was linearly correlated to the number of islets (N = 12, P less than 0.01), indicating that insulin did not significantly inhibit its own secretion in this system. Finally, during glucose stimulation, the insulin concentration in the effluent from the chamber was found to be four times the concentration present at the turning point of the blood channel, suggesting that insulin was transferred into the perfusing medium in part by a countercurrent flux of ultrafiltrate crossing the membranes. We present herein the kinetic modelling of glucose and insulin transfer in this "ultrafiltration chamber," whose functional characteristics are compatible with closed-loop insulin delivery.

Animals

In vitro study of combined convection- diffusion mass transfer in hemodialysers.

Clearance measurements have been obtained for urea, Vit B12 and myoglobin by simultaneous hemodialysis and ultrafiltration (UF) techniques, using various commercially available hemodialysers. The experimental results confirm that the overall clearance is less than the clearance of each process occurring separately due to interaction between convection and diffusion. Adequate urea clearance (100 ml/min) can be obtained either by using high ultrafiltration (60 ml/min) with low dialysate flow rate (70 ml/min) or moderate ultrafiltration (less than 30 ml/min) with higher dialysate flow rate (120 ml/min). The comparison of experimental clearance with the predictions of theoretical model (1) for urea are found to be in good agreement for dialysate flow rates of more than 300 ml/min and for smaller dialysate flow rates the predicted clearances are higher than measured ones. An approximate correlation for the overall clearance is CL = CLD + QF/2 where CLD is the dialytic clearance and QF the UF flow rate.

Blood

Forward and backward waves in the arterial system, their relationship to pressure waves form.

The purpose of this work was to analyze, in human subjects, the shape of the aortic pressure wave from its forward and backward components calculated by use of Westerhof's model. Twenty-nine patients were studied: 11 normal subjects, 11 hypertensive patients and 7 patients with congestive heart failure. The following measurements and calculations were performed both under control conditions and during either angiotensin infusion in 5 normal subjects or nitroprusside infusion in 6 hypertensive patients: cardiac output, aortic blood pressure (catheter tip micromanometer), blood flow velocity (electromagnetic catheter-tip velocity transducer) in the ascending aorta, aortic impedance and reflection coefficients allowing the calculation of the aortic forward and backward pressure waves. The results show that the shape of aortic pressure wave in hypertensive patients is related to increased arterial wall stiffness which determines greater values and overlap of the forward and backward waves. This result is corroborated by the changes observed during angiotensin infusion in normal subjects. The shape of pressure wave in heart failure patients is dicrotic. This shape is related to smaller values and overlap of forward and backward waves. This appears related to a reduced stroke volume. During peripheral vasodilation the shape of pressure wave in hypertensive patients becomes dicrotic. However, this was mainly related to later backward waves. These results confirm that the shape of pressure waves depends both on the arterial wall stiffness and on the left ventricular performance: mainly on the stroke volume. The calculation of forward and backward waves allows a quantitative analysis of pressure waves.

Adult