New methods for hemoglobin detection in a microparticle-plasma suspension

In the extracorporeal adsorption system, MDS (Microspheres based Detoxification System), micro-adsorbent particles measuring 1-25 micrometers circulate in a filtrate circuit for highly specific blood purification/adsorption. The MDS circuit containing the adsorbent microparticles is linked to the patient's blood line by a hollow fiber plasma filter. When the transmembrane pressure or the shear forces due to the red blood cells in the hollow fiber filter are too high, they can be damaged and hemoglobin will be released. In order to detect free hemoglobin (fHb) by optical means, we have designed a new flow-dynamic filter system, placed in the microadsorbent circuit for continuous separation of microparticles from the filtrate. In the flow dynamic filter, we use a high velocity liquid vortex to remove sedimentation and particle plugs on the filter membrane. In our investigations, 3 and 8 micron cellulose nitrate filter membranes for particle separation are used. The obtained particle free bypass filtrate flow rates are typically 0.5 and 0.8 ml/min respectively. The typical sensitivity for fHb detection by the applied noninvasive optical method is 0.15 g/dL. Medical safety regulations require a fail-safe mechanism for fHb detection which monitors the bypass filtrate flow in the flowdynamic filter and shuts down the system in case of membrane occlusion. The bypass filtrate flow is monitored by periodically occluding and releasing the bypass line by means of a clamp. The resulting back pressure profile gives information about the actual filtration rate. This safety principle was proven by statistical analysis and shows its clear functionality.     

外部作用力引起组织压动态变化时的毛细血管血流

建立了组织压随中医推拿摆动类手法作用力发生动态变化时的毛细血管 -组织血液动力学模型 ,以此来解释中医推拿摆动类手法的血液动力学机制。血液在毛细血管内作低雷诺数流动 ,血浆渗出毛细血管壁遵循Starling定律 ,组织压随实测的滚法推拿作用力线性变化。同时考虑了血液表观黏度、血浆蛋白浓度、红细胞压积。数值计算了组织压动态变化时的毛细血管流量、血液表观黏度、渗透率和渗透因子 ,并和静态组织压的相应变量进行比较。结果显示 ,组织压动态变化导致毛细血管血流量有所增大 ,而血液表观黏度将下降 ,定性说明了中医摆动类手法的“活血化瘀”血液动力学机制。     

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.     

Renal corpuscular hydrodynamics: Digital computer simulation

Summary A mathematical model of the renal corpuscle is presented and used to quantify the effect on filtration rate, nephron blood flow and hydrostatic pressure in the glomerular capillaries of variations in: 1. the hydrostatic pressure in Bowman's space; 2. the hydrodynamic resistances of the afferent and efferent arterioles; 3. the ultrafiltration coefficient of the glomerular membrane; 4. the hydrostatic pressure in the peritubular capillaries; 5. the arterial haematocrit and plasma protein concentration. The model is derived from the principle of conservation of mass and volume. Hydrostatic pressure gradients along the glomerular capillaries are neglectec. The hydrodynamic resistances of the afferent and efferent arterioles are assumed to be determined by two independent factors, one being determined by the vascular dimensions, the other by the haematocrit. Blood flow is considered to be related in a linear manner to the hydrostatic pressure decreases along these vessels. The effect of changing the hydrostatic pressure in Bowman's space on nephronGFR was calculated and found to agree with experimental measurements. When corpuscular hydrodynamics are related to variations in the hydrodynamic resistance of the afferent or efferent arteriole it is seen that the change in efferent arteriolar plasma flow accompanying altered nephronGFR is very sensitive to the way in which the change is produced. In contrast changes in glomerular capillary pressure and filtration fraction are insensitive. The calculations indicate that differences measured in nephronGFR between superficial and juxtamedullary nephrons can be explained by assuming that the diameters of the afferent and efferent arterioles of the juxtamedullary nephrons increase in direct proportion to the diameter of the renal corpuscle.     

Neural control of nutritional and nonnutritional circuits in the dog hindpaw

The neural control of blood flow and volume distribution between parallel nutritional and nonnutritional circuits has been investigated in the vascularly and neurally isolated dog hindpaw. Twelve paws were perfused by controlled pressure and ten paws were perfused by controlled flow via the cranial tibial artery. Venous outflow was measured and collected from the lateral saphenous vein. The superficial and deep fibular nerves and the tibial nerve were cut and individually stimulated, resulting in rates which at least doubled the blood flow resistance. Vascular volume changes were measured by injections of 51Cr-labeled red cells and 131I-labeled albumin. Tissue volume changes were measured by plethysmography. Capillary diffusion capacity was calculated from 86Rb extractions, and capillary filtration coefficients were determined. Superficial fibular nerve and deep fibular nerve stimulations apparently resulted in nonnutritional circuit constriction with resulting blood flow redistribution to nutritional circuits, possibly located in tissues other than the skin, e.g., adipose tissue. Tibial nerve stimulation caused no redistribution of blood flow between the two circuits presumably due to a uniform constriction of arteries and small vessel segments.     

Fast Estimation of Arterial Vascular Parameters for Transient and Steady Beats with Application to Hemodynamic State under Variant Gravitational Conditions

Numerous parameter estimation techniques exist for characterizing the arterial system using electrical circuit analogs. These techniques are often limited by requiring steady-state beat conditions and can be computationally expensive. Therefore, a new method was developed to estimate arterial parameters during steady and transient beat conditions. A four-element electrical analog circuit was used to model the arterial system. The input impedance equations for this model were derived and reduced to their real and imaginary components. Next, the physiological input impedance was calculated by computing fast Fourier transforms of physiological aortic pressure (AoP) and aortic flow. The approach was to reduce the error between the calculated model impedance and the physiological arterial impedance using a Jacobian matrix technique which iteratively adjusted arterial parameter values. This technique also included algorithms for estimating physiological arterial parameters for nonsteady physiological AoP beats. The method was insensitive to initial parameter estimates and to small errors in the physiological impedance coefficients. When the estimation technique was applied to in vivo data containing steady and transient beats it reliably estimated Windkessel arterial parameters under a wide range of physiological conditions. Further, this method appears to be more computationally efficient compared to time-domain approaches. © 1999 Biomedical Engineering Society. PAC99: 8719Uv, 8710+e, 0230Qy     

Quantification of aortic regurgitation by Doppler echocardiography: a new method evaluated in pigs

We have developed a method to quantify aortic regurgitant orifice and volume, based on measurements of the velocity of the regurgitant jet, aortic systolic flow, the systolic and diastolic arterial pressures, a Windkessel arterial model, and a parameter estimation technique. In six pigs we produced aortic regurgitant flows between 2·1 and 17·8 ml per beat, i.e. regurgitant fractions from 0·06 to 0·58. Pulmonary and aortic flows were measured with electromagnetic flow probes, aortic pressure was measured invasively, and the regurgitant jet velocity was obtained with continuous-wave Doppler. The parameter estimation procedure was based on the Kalman filter principle, resulting primarily in an estimate of the regurgitant orifice area. The area was multiplied by the velocity integral of the regurgitant jet to estimate regurgitant volume. A strong correlation was found between the regurgitant volumes obtained by parameter estimation and the electromagnetic flow measurement. These results from our study in pigs suggest that it may be possible to quantify regurgitant orifice and volume in patients completely noninvasively from Doppler and blood pressure measurements.     

Vascular recruitment in forearm muscles during exercise

Blood flow and filtration of water across the vascular bed in human forearm muscles were studied at rest and during graded exercise with a hand ergometer. Blood flow was measured by dye dilution and water filtration was determined after injection of hyperoncotic albumin solution (23%) in the brachial artery creating a tissue to blood ultrafiltration measureable as a dilution in the effluent blood. The filtration constants were expressed as a filtration coefficient Fc (ml water/ml plasma mmHg increase in oncotic pressure), and, multiplying by the plasma flow, as a filtration capacity Kf (ml water/100 ml tissue min mmHg increase in oncotic pressure). During the increase in plasma flow induced by exercise, Fc remained constant at about 0.0007, but Kf increased in parallel with the hyperaemia from 0.0031 to 0.038 when plasma flow increased from 4 to 48 ml (100 ml min)-1. The data suggest a more massive recruitment of exchange area during exercise (a factor 12) than suspected on the basis of ultrafiltration in animals made with the prolonged venous stasis technique (showing a factor 2-5). The estimated variability in exchange surface area indicates, that animal studies of muscle circulation, whether pertaining to capillary permeability or capillary filtration should gain by an independent estimate of the number of capillaries that are flowing during the particular experimental situation.     

Renal function in juvenile rats subjected to prenatal malnutrition and chronic salt overload

Dietary sodium may contribute to hypertension and to cardiovascular and renal disease if a primary deficiency of the kidney to excrete sodium exists. In order to investigate whether chronic 1% NaCl in the drinking water changes blood pressure and renal haemodynamics in juvenile Wistar rats subjected to prenatal malnutrition, an evaluation of plasma volume, oxidative stress in the kidney, proteinuria and renal haemodynamics was carried out. Malnutrition was induced by a multideficient diet. Mean arterial pressure, renal blood flow and glomerular filtration rate (GFR) were measured using a blood pressure transducer, a flow probe and inulin clearance, respectively. Plasma volume and oxidative stress were measured by means of the Evans Blue method and by monitoring thiobarbituric acid reactive substances (TBARS) in the kidneys, respectively. Urinary protein was measured by precipitation with 3% sulphosalicylic acid. It was observed that prenatally malnourished rats presented higher values of plasma volume (26%, P < 0.05), kidney TBARS (43%, P < 0.01) and blood pressure (10%, P < 0.01) when compared with the control group. However, they showed no change in renal haemodynamics or proteinuria. Neither prenatally malnourished nor control rats treated with sodium overload presented plasma volume or blood pressure values different from their respective control groups, but both groups presented elevated proteinuria (P < 0.01). The prenatally malnourished group treated with sodium overload presented higher values of kidney TBARS, GFR and filtration fraction (58, 87 and 72% higher, respectively, P < 0.01) than its respective control group. In summary, sodium overload did not exacerbate the hypertension in juvenile prenatally malnourished rats, but induced renal haemodynamic adjustments compatible with the development of renal disease.     

Display stabilising circuit for systolic-diastolic blood-pressure monitors

When using a digital panel meter to display blood pressure, it is difficult to achieve a stable, clinically usable display. A circuit is described, which allows the measured parameter to be displayed in a stable manner ignoring small beat-to-beat variations. The described circuit and a systolic-diastolic separator provide the complete circuitry for a low-cost instrument for the the numerical display of arterial blood pressure.     

Pulsing reverse osmosis as the mechanism underlying fluid exchange.

Problems inherent in the existing theories of fluid exchange are discussed. An alternative theory based on the interaction between the pulsing of the capillary pressure and the osmotic gradient between plasma and interstitial fluid is offered. Theoretic values for plasma and interstitial osmolalities are calculated. These are similar to the pressure found in the Bowman's capsule in the kidney. The theory offers a possible explanation for the pulsatile nature of the blood pressure, the formation of oedema and the stasis of fluid exchange in shock.     

The influence of HES on the filtration properties of capillary membrane plasmaseparation

Plasmaseparation is a treatment under discussion for critically ill patients, especially in sepsis and multiorgan failure. These patients receive a variety of different fluid substitutes, including hydroxyethylstarch (HES). HES is known to influence rheological properties, but nothing is known about the possible interactions between HES and the plamaseparation procedure. We used an in vitro plasmaseparation circuit with heparinized porcine blood. Before priming the system, 2 liters of blood were supplemented by adding 100 ml of either NaCl 0.9% or HES (n=6 in each group). We monitored the transmembrane (TMP) and the filtration pressure (PF) and measured free plasma hemoglobin (free Hb) and platelet counts before and after the two hours plasmaseparation procedure. The final transmembrane pressure was significantly higher with HES substitution. In the HES group we found negative filtration pressures from the very beginning with a significant further decrease toward the end of the experiments. A significant increase in free Hb and decrease in platelet counts were noted only in the HES group. Volume substitution with HES leads to impaired filtration properties and deteriorated hemocompatibility in in vitro plasmaseparation. Further studies have yet to evaluate whether or not the effects described also occur under clinical conditions.     

Optimization of the wedge filter parameters for a radiotherapy treatment planning system

When a treatment planning system uses an empirical or semianalytical approach to describe the influence of a wedge filter on a photon beam, a number of experimentally determined parameters are required. These may be found from direct measurement. However, if the beam model is sensitive to the parameters, it will be necessary to optimize the parameter values to obtain better correspondence between dose profiles calculated by the model and actual measured profiles. The procedure is time consuming if optimization is done manually. We have developed an optimization scheme, using a personal computer, to find the set of wedge parameters which will result in the best fit of calculated wedge profiles (using the beam model of the treatment planning system) to measured wedge profiles. The procedure is efficient and calculated profiles were found to match measured profiles to within 2% of the central axis value.     

Fibrinogen synthesis stimulation by prostaglandin E1 and some other vasodilators.

Three-hour constant-rate intravenous infusion into rabbits of 1-3 mg prostaglandin E1 (PGE1) per kilogram markedly increased plasma fibrinogen 24 h later. 131I-labeled fibrinogen and model studies showed increased synthesis underlay this. Similar PGE1 doses lowered systolic blood pressure. Maintaining systolic blood pressure by infusing noradrenaline with the PGE1 did not alter plasma fibrinogen response to PGE1; plasma fibrinogen was unchanged by noradrenaline infusion. Regression equations relating plasma fibrinogen increment to PGE1 dose, plasma fibrinogen increment to dose and systolic blood pressure change, and systolic blood pressure change to dose are given as well as the constants relating plasma fibrinogen increment to dose using the Michaelis-Menten equation. Infusions of cyclic AMP, dibutyryl cyclic AMP, and cyclic GMP intravenously led to only small plasma fibrinogen increases. Daily intravenous infusions of PGE1 led to loss of both plasma fibrinogen and systolic blood pressure responses in two animals; a third animal showed only loss of the former and a fourth only loss of the latter response. PGE1 slightly enhanced the small plasma fibrinogen increase following intravenous bradykinin. Approximate arterial blood PGE1 concentrations resulting from the intravenous infusion of 1 mg mg PGE1 kg-1 3 h-1 are calculated. These are compared with measured values.     

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.     

Asymmetric membrane filters for the removal of leukocytes from blood.

As part of a study on the mechanisms of leukocyte filtration, the influence of pore size distribution on filter efficiency was investigated. Conventional leukocyte filters are not suitable for model studies, as these filters are composed of tightly packed synthetic fibers, with a poorly defined porous structure. Therefore, open cellular polyurethane membranes with pore size distributions varying from approximately 15 to 65 microns were prepared. Filtration experiments with stacked packages of these membranes showed that leukocytes are best removed (greater than 99%) by filters with a pore size distribution of 11-19 microns. These pore sizes approach the size of leukocytes (6-12 microns). However, due to fast clogging, blood flow through these filters is rapidly reduced, which results in a low filter capacity. With an asymmetric membrane filter, in which the pore size decreases from about 65 to 15 microns in the direction of blood flow, both moderate removal of leukocytes (greater than 80%) and maintenance of flow (approximately 0.2 mL/s) are obtained. This results in efficient leukocyte removal. From cell analysis of both filtrate and filter, it is concluded that adhesion rather than sieving is the major filtration mechanism. Thus, further optimization of the filter may be achieved by surface modification.     

Membrane plasma fractionation: effect of the surface area

The influence of the surface area on the performance of plasma filters for dead-end mode of filtration is presented in this paper. Theoretical analysis of the dead-end filtration was performed and verified experimentally (using ENKA cellulose-diacetate PF-100 membranes) in respect to beta-lipoprotein. The theoretical model allows to optimize the course of the transmembrane pressure during plasma fractionation procedure in dependence of the surface area, initial concentration of macromolecules, total volume of the feed and membrane structure. The results indicate that the surface area effect is an important factor in the operation of membrane plasma fractionation and should be considered in the design of the plasma fractionation filter.     

多频率阻抗法研究血液电特性

根据血液的阻抗－频率特性和典型的三元件血液模型，介绍了一种研究血液电特性的新方法多频率阻抗法。并对用生理盐水置换了血浆的血液和经戊二醛磷酸缓冲液处理后，红细胞硬化的血液的电特性进行了实验研究。结果表明，新方法采用的血浆电阻Ｒ０，红细胞内液电阻Ｒ１和细胞膜电容Ｃ参数等能高灵敏地反映血浆、红细胞内液及细胞膜等的状态及性能变化，可为全面评价血液特性提供一种有效的手段。     

Compared study of micro-aggregates filters (output, filtration pressure and study of the deposit with scanning electron microscopy) (author's transl)]

Special filters for the elimination of cellular aggregates were conceived especially to prevent pulmonary complications in patients shocked particularly after massive transfusions as well as to prevent cerebral complications after extra-corporeal circulation. The performances and the conditions of use of these filters (perfusion output, change of the filter) were considered. Four filters were carefully studied: the Fenwal filter, the Swank filter, the Biotest filter and the intersep Johnson and Johnson filter. The following studies were carried out for each filter: the perfusion output (of three bottles filtered one after another with or without pressure); the filtration pressure (Swank technique) of the whole blood up-and-down filter; the viscosity and various hematologic parameters (NF, hemoglobin and gobular ATP); finally, the deposit was studied morphologically with scanning electron microscopy. It appeared that a good capacity of aggregates elimination (decrease of the filtration pressure of 95%) was often linked to a feeble output and the necessity of replacing the filter. The efficacy of the Fenwal filter, the Swank filter, the Biotest filter and the intersept filter was practically the same, but the Intersept filter provided the best output with an equal filtration capacity. The other parameters remained about the same. The deposits included fibrinogen, deformed red blood corpuscules (echinocytes), leucocytes and platelets.     

Two models of glomerular filtration rate and renal blood flow in the rat

Two mathematical models of glomerular filtration and blood flow are derived. The first is based on principles of fluid and mass conservation in individual capillaries. The model explains why the filtration rate (GFR) is strongly dependent on local hydrostatic and protein oncotic pressures, and on plasma flow rate (GCPF), but only weakly dependent on exact numbers, lengths, radii, or filtration coefficient of glomerular capillaries. The model shows that much of the increased GFR in both isooncotic plasma loading and isotonic Ringer's loading is due to increased GCPF caused by diluting erythrocytes. The second model uses several approximations and reduces to a quadratic in afferent arteriolar blood flow. When arterial pressure, hematocrit, plasma protein concentration, and afferent and efferent arteriolar resistances are specified, the model predicts GFR, afferent arteriolar blood flow, and filtration fraction. Alternatively, if any two of these three variables are known, the model predicts segmental arteriolar resistances. The model indicates that GFR and blood flow regulation must be located in the afferent arteriole, despite the strong dependence of GFR on GCPF.