PubMed HealthSearch

Biomedical subjects

B Rippe

Publications and source records attributed to B Rippe.

At least 37 records · Page 2Linked to original sources

Osmotic barrier properties of the rat peritoneal membrane.

In this study the osmotic barrier characteristics of the rat peritoneal membrane were investigated. Fluid movements between the peritoneal cavity and the blood were measured following instillation of isotonic saline (control) and hypertonic solutions of NaCl, glucose, sucrose, raffinose and myoglobin (test solutions). Moreover, 5 and 8% albumin in NaCl were investigated. Osmotic transients were assessed using a simple volume recovery technique. Peritoneal osmotic conductances (i.e. products of peritoneal hydraulic conductances [LpS] and solute reflection coefficients [sigma]) were calculated from the differences in the rates of peritoneal fluid loss and in osmotic pressures between test solutions and the isotonic saline control solution. The osmotic conductance to glucose was estimated to be 1.63 microliters min-1 mmHg-1 m-2 and that for albumin to be 59.6 microliters min-1 mmHg-1 m-2. Assuming an albumin sigma of 0.9, the sigma of glucose was estimated to be 0.025, in accordance with previous measurements for the cat peritoneal membrane. The osmotic conductances assessed here were compatible with an 'overall' peritoneal equivalent small pore radius of 47-48 A, but could also be fitted to a three-pore model of peritoneal permselectivity, including a transcellular (ultra-small pore) pathway and a large pore pathway. The great discrepancy between peritoneal sigma for small solutes and that for albumin obtained in this study indicates that small solute reflection coefficients are close to zero while that for albumin is not far from unity. Furthermore, the peritoneal hydraulic conductance (ultrafiltration coefficient) is large enough to allow for a substantial absorption of fluid directly into the plasma when the crystalloid osmotic pressures in blood and peritoneal dialysate are in equilibrium.

Albumins

A three-pore model of peritoneal transport.

The three-pore model of peritoneal transport treats the capillary membrane as a primary barrier determining the amount of solute that transports to the interstitium and the peritoneal cavity. According to the three-pore model, the principal peritoneal exchange route for water and water-soluble substances is a protein-restrictive pore pathway of radius 40-55 A, accounting for approximately 99% of the total exchange (pore) area and approximately 90% of the total peritoneal ultrafiltration (UF) coefficient (LpS). For their passage through the peritoneal membrane proteins are confined to so-called "large pores" of radius approximately 250 A, which are extremely few in number (0.01% of the total pore population) and more or less nonrestrictive with respect to protein transport. The third pathway of the three-pore model accounts for only about 2% of the total LpS and is permeable to water but impermeable to solutes, a so-called "water-only" (transcellular?) pathway. In contrast to the classical Pyle-Popovich (P&P) model, the three-pore model can predict with reasonable accuracy not only the transport of water and "small solutes" (molecular radius 2.3-15 A) and "intermediate-size" solutes (radius 15-36 A), but also the transport of albumin (radius 36 A) and larger molecules across the peritoneal membrane. The model operates with reflection coefficients(a) (sigma's) for small solutes < 0.1. These are approximately one order of magnitude lower than the sigma's in the P&P model. Furthermore, the peritoneal LpS is one order of magnitude higher than in the P&P model.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport

Glomerular permselectivity is dependent on adequate serum concentrations of orosomucoid.

Orosomucoid, or alpha 1-acid glycoprotein, a serum protein known to be an "acute phase reactant" has recently been shown to be needed for the maintenance of normal capillary permeability in skeletal muscle and mesentery. Therefore, we were interested in studying whether the glomerular capillary wall is affected by orosomucoid as well. For this purpose, left and right kidneys from nine rats (group A) were isolated and perfused in situ and in parallel using separate solutions of human albumin (1.8% in Tyrode), differing in their content of orosomucoid, one containing 0.21 g/liter, the other less than 0.005 g/liter. The temperature was kept at 8 degrees C in order to minimize tubular reabsorption of fluid and albumin. The two kidneys showed identical and stable vascular resistances during the experiments. Also the glomerular filtration rates (GFR) were stable between 30 and 33 ml/min/100 g kidney. Initially, the two kidneys showed similar fractional albumin clearance (theta) values of approximately 0.003. However, in the "absence" of orosomucoid theta increased to become four- to fivefold higher in the test kidney than in the control kidney at the end of the 1 1/2 hour experiment. This difference was observed in all rats, suggesting that orosomucoid is needed also for the maintenance of the glomerular permselectivity. In a separate group of eight animals (group B), orosomucoid-containing albumin solutions were used in parallel with horse serum solutions to perfuse the two kidneys of each rat, at 8 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Tissue uptake of insulin and inulin in red and white skeletal muscle in vivo.

By employing a tissue uptake technique, the kinetics of the plasma-interstitial equilibration of radiolabeled insulin, inulin, and albumin were followed in four muscles of differing capillarity in anesthetized rats. The soleus muscle (SOL), and the red portion of the gastrocnemius muscle (RG), as well as the extensor digitorum longus muscle (EDL) and the white portion of the gastrocnemius muscle (WG) were investigated. After constant intravenous tracer infusions and repeated plasma sampling under euglycemic clamp conditions, animals were killed at varying time intervals and the muscles mentioned above were dissected out. The radioactivity of tracer per gram of tissue in each muscle divided by the plasma activity of tracer per milliliter of plasma, i.e., "the plasma equivalent space" of tracer, thus could be followed as a function of time. From this function the permeability-surface area (PS) of inulin as well as the distribution volumes at time 0 (V0) of inulin and insulin and their equilibrium distribution volumes (VE) were assessed. The PS for inulin (in ml.min-1.100 g muscle-1) was 0.52 +/- 0.10 (mean +/- SE) in WG, increasing with more red fibers to 1.37 +/- 0.18 in SOL. Also the inulin interstitial distribution volume (at blood-tissue tracer equilibrium; VE) increased in this order (in ml/100 g) from 7.30 +/- 0.91 in WG to 12.93 +/- 0.89 in SOL. The V0 for insulin was found to be approximately fivefold larger than the plasma volume in each muscle sample, indicating a high degree of binding of insulin to structures within the vascular compartment, conceivably to the vascular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Lymphatic versus nonlymphatic fluid absorption from the peritoneal cavity as related to the peritoneal ultrafiltration capacity and sieving properties.

In this article we discuss the role of capillary fluid absorption via Starling mechanisms (the transcapillary hydrostatic pressure gradient opposed by the colloid osmotic pressure gradient as multiplied by the capillary UF coefficient) vs. lymphatic fluid absorption as determinants of the total fluid loss from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD). We also mention that, under nonsteady state conditions, there is in addition some net absorption of fluid into the interstitium of tissues surrounding the peritoneal cavity. Support for the contention that nonlymphatic fluid absorption directly into the capillaries is the major mode of fluid transport from the peritoneal cavity to the blood is given by measurements of the peritoneal-to-blood clearance of tracer albumin (or other proteins). Such measurements yield clearance values of the order of 0.2-0.3 ml/min in CAPD. This represents only about 20% of the total peritoneal fluid loss rate (1.2-1.3 ml/min) in ordinary CAPD dwells. Indirect support for a relatively low lymph flow is also derived from capillary physiology. Like continuous capillary walls, the peritoneal membrane shows a bimodal selectivity towards molecules of graded molecular size. Thus, small solute transport can be described as occurring by diffusion through numerous 'small' (approximately 50 A radius) pores, whereas large solute transport is consistent with blood-peritoneal convection through smaller numbers of 'large' (radius approximately 250 A) pores. Furthermore, peritoneal sieving data are compatible with the notion that large crystalloid osmotic pressure gradients cause fluid flow through a water-exclusive ('ultra-small' pore) pathway. A three-pore model of peritoneal selectivity can explain why small solute sieving coefficients are only 0.5-0.6, even though small solute reflection coefficients are close to zero. Another important implication of the three-pore concept is that the peritoneal UF-coefficient is much higher than previously thought, emphasizing the role of capillary absorption in the fluid loss from the peritoneal cavity in CAPD. It is concluded that fluid loss from the peritoneal cavity is dominated by capillary fluid absorption. Hence, lymphatic absorption accounts for just a small fraction of the peritoneal-to-blood absorption of fluid in peritoneal dialysis.

Absorption

Net fluid absorption under membrane transport models of peritoneal dialysis.

The effect of oncotic pressure and lymphatic flow on intraperitoneal dialysate volumes in peritoneal dialysis is investigated under each of two membrane transport models: one assuming a homogeneous single-pore membrane and the other a heteroporous three-pore membrane. In both cases, solute and fluid removal are assumed to occur via a mass transport model in which the peritoneum acts like a synthetic membrane separating two well-mixed compartments (body and dialysate). The homoporous mass transport model of Pyle and Popovich and the three-pore model of Rippe et al., although conceptually different, are shown to be equivalent mathematically. This feature allows one to apply the analytical solutions of Vonesh et al. to either model. It also enables one to apply parameter estimates from one model to another; for example, one can apply the lumped sum reflection coefficients of the three-pore model to a homoporous membrane model. A comparison is made between the use of empirically estimated rejection coefficients computed under the homoporous membrane model of Pyle and Popovich versus lumped-sum reflection coefficients calculated in accordance with the three-pore model of Rippe et al. The two models predict similar drain volumes provided the exchange is conducted using glucose as the osmotic agent. However, one does see a significantly different contribution of protein oncotic pressure and lymphatic drainage to fluid absorption under the two sets of osmotic reflection coefficients. Moreover, for a simulated exchange employing an osmotic agent with a molecular weight of 20,000 daltons, the use of reflection coefficients calculated under the three-pore model yields net ultrafiltration values which are more consistent and physiological than results obtained using the empirically estimated rejection coefficients. Since estimates of 'lymphatic flow' will vary according to the quantity and quality of input parameter values (i.e., hydrostatic pressure, protein concentrations, osmotic reflection coefficients), it would be better to label these estimates as the sum of lymphatic and unmodeled net fluid absorption.

Ascitic Fluid

Computer simulations of peritoneal fluid transport in CAPD.

To model the changes in intraperitoneal dialysate volume (IPV) occurring over dwell time under various conditions in continuous ambulatory peritoneal dialysis (CAPD), we have, using a personal computer (PC), numerically integrated the phenomenological equations that describe the net ultrafiltration (UF) flow existing across the peritoneal membrane in every moment of a dwell. Computer modelling was performed according to a three-pore model of membrane selectivity as based on current concepts in capillary physiology. This model comprises small "paracellular" pores (radius approximately 47 A) and "large" pores (radius approximately 250 A), together accounting for approximately 98% of the total UF-coefficient (LpS), and also "transcellular" pores (pore radius approximately 4 to 5 A) accounting for 1.5% of LpS. Simulated curves made a good fit to IPV versus time data obtained experimentally in adult patients, using either 1.36 or 3.86% glucose dialysis solutions, under control conditions; when the peritoneal UF-coefficient was set to 0.082 ml/min/mm Hg, the glucose reflection coefficient was 0.043 and the peritoneal lymph flow was set to 0.3 ml/min. Also, theoretical predictions regarding the IPV versus time curves agreed well with the computer simulated results for perturbed values of effective peritoneal surface area, LpS, glucose permeability-surface area product (PS or "MTAC"), intraperitoneal dialysate volume and dialysate glucose concentration. Thus, increasing the peritoneal surface area caused the IPV versus time curves to peak earlier than during control, while the maximal volume ultrafiltered was not markedly affected. However, increasing the glucose PS caused both a reduction in the IPV versus time curve "peak time" and in the "peak height" of the curves. The latter pattern was also seen when the dialysate volume was reduced. It is suggested that computer modelling based on a three-pore model of membrane selectivity may be a useful tool for describing the IPV versus time relationships under various conditions in CAPD.

Ascitic Fluid

A note on the errors of using venous congestion in intact rats for determinations of microvascular permeability.

The established ideas of transcapillary exchange have recently been challenged based on studies in intact rats. In vivo measurements of net fluid flux and albumin clearance in muscle (and skin) have given estimates of the reflection coefficient (sigma) for albumin of 0.98-0.99 compared to the sigma value of 0.90 obtained by most other techniques. This discrepancy has vast consequences for the understanding of the transcapillary passage of macromolecules. A sigma for albumin near unity implies that there is virtually no coupling between protein and fluid transfer as induced by, for example, increases in vascular hydrostatic pressures. However, there are several assumptions inherent in the seemingly straight-forward experiments on intact rats, and in the present study we tested the hypothesis that occlusion of the femoral vein by ligation induces only moderate and transient increments of venous pressure (PV). During control conditions PV was 6.3 mmHg and pressure increased to 12.8 mmHg immediately following venous occlusion. However, PV declined with time and after 30 minutes of occlusion the capillary hydrostatic pressure was only increased by 3.0 mmHg. Calculations of the capillary filtration coefficient gave completely unrealistic values, close to those of maximally vasodilated skeletal muscle. The findings suggest that data obtained from intact rats, albeit important and interesting, should be evaluated with great care due to possible experimental errors in the in vivo approaches. In particular, the technique of estimating sigma for albumin in intact rats must be subjected to modifications before allowing any reliable conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins

Upper and lower bounds on capillary permeability ratios of Cr-EDTA to cyanocobalamin in rat hindquarters.

The single injection indicator dilution technique, often used for assessing capillary permeability, was employed for estimations of the equivalent pore radius of skeletal muscle microvessels according to the theory of restricted diffusion. There are, however, certain important sources of error that must be considered in order to allow conclusions regarding the degree of restricted diffusion. In this study, we have recalculated previously published data in order to minimize the effect of heterogeneity of the second kind, i.e. a transit-time dependence of the fractional extraction values. The method used makes it possible to calculate reliable intervals of confidence for the permeability surface area products, and hence for the permeability surface area product-ratios (and equivalent pore radius), taking into account the maximal theoretical impact of back diffusion on measured extraction data. After correction for transit-time dependent effects of heterogeneity, the permeability surface area product-ratio of Cr-EDTA to cyanocobalamin (vit. B12) from 48 measurements in eight rats was found to have a theoretical 'upper bound' of 2.63 +/- 0.06 and a lower bound of 2.10 +/- 0.07, corresponding to an equivalent pore radius of 60 to 109 A. This minimum pore radius estimate was even further reduced by corrections for plasma flow dependent reductions in overall extraction fraction (heterogeneity of the first kind) to 45 A, whereas the upper bound on pore radius was reduced to 60 A. These data strongly support the presence of marked restricted diffusion of small solutes in the maximally vasodilated rat hindquarter microvasculature.

Animals

Clinical implications of a three-pore model of peritoneal transport.

The peritoneal barrier exchange characteristics are in this article described in terms of a three-pore model of membrane permselectivity. The peritoneal membrane during continuous ambulatory peritoneal dialysis (CAPD) is thus simulated to have a large number of small pores of radius 40-55 A, a small number of large pores of radius 200-300 A, and an abundance of transcellular pores of radius 4-5 A. Due to the heteroporous nature of the peritoneal membrane, peritoneal small solute sieving coefficients are of the order of 0.5-0.6, and not near unity, as predicted for a homoporous membrane having 50 A (radius) equivalent pores, but lacking transcellular pores. As a consequence, the dialysate during CAPD is diluted during the first 50-100 minutes of the dwell. Furthermore, there is a marked coupling between the increased net transperitoneal volume flow, occurring early in the cycle, and the transfer of "small" macromolecules, such as beta 2-microglobulin and albumin, across the peritoneal membrane. This coupling is, however, small for "large" macromolecules, such as IgG and IgM, or for small solutes. Increasing the peritoneal surface area, in computer simulations of peritoneal transport according to the three-pore model, causes the simulated intraperitoneal (i.p.) volume vs. time (V(t)) curves to peak earlier than during control, while the maximum volume ultrafiltered is not markedly affected. However, selectively increasing the glucose PS (mass transfer area coefficient) causes a reduction both in the peak time and the peak "height" of the V(t) curves. The latter pattern is also seen when the dialysate volume is reduced. It is concluded that a three-pore model of membrane permselectivity selectivity can adequately describe the kinetics of peritoneal transport of small and large solutes and of fluid.

Ascitic Fluid

A phenomenological interpretation of the variation in dialysate volume with dwell time in CAPD.

Intraperitoneal fluid volume (IPV) changes versus time were followed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using a simple volume recovery method. In each patient dialysates containing 1.36 and 3.86 percent glucose as an osmotic agent were investigated. The patients' IPV versus time data were fitted to a function determined by four "arbitrary" coefficients, from which both the initial ultrafiltration (UF) rate immediately following intraperitoneal (i.p.) fluid instillation and the "final" peritoneal-to-blood fluid absorption rate could be assessed. The peritoneal osmotic conductance to glucose, that is, the peritoneal ultrafiltration coefficient (Kf), times the peritoneal osmotic reflection coefficient to glucose (sigma g), Kf sigma g, was determined using two related approaches. Kf sigma g is a major determinant of the transperitoneal volume exchange, and it was calculated to be 3.54 +/- 0.85 (+/- SE) and 3.81 +/- 0.52 microliters/min/mm Hg, respectively, depending on the assumption employed. Kf sigma g was further analysed according to a three-pore model of membrane permeability to determine the possible range of Kf and sigma g compatible with a peritoneal small solute sieving coefficient (phi) ranging from 0.3 to 0.61. According to these calculations both Kf and sigma g ranged from 0.043 to 0.081 (ml/min/mm Hg and dimensionless, respectively). The maximal peritoneal lymph flow (L) realistic according to this analysis, and compatible with a measured total peritoneal-to-blood fluid absorption rate of 1.25 +/- 0.14 ml/min, was 0.75 ml/min, the most plausible values, however, falling between 0.3 to 0.5 ml/min.

Biological Transport

Vascular clearance by the reticuloendothelial system--measurements using two different-sized albumin colloids.

Normal and reticuloendothelial system (RES) stimulated rats were examined with dynamic liver RES scintigraphy using a computerized gamma camera. 99Tcm-labelled albumin colloid, albures (radius 250 nm) or nanocoll (radius 25 nm), or both were used as test substances to study the kinetics of vascular clearance after RES stimulation. Registrations were made of 30 s per frame for 5 min and 300 s per frame for 15 min or 25 min and a region of interest (ROI) was indicated over the liver. Whole body and liver RES clearance rate constants (k) were calculated from the liver uptake vs time curve. Liver parenchyma blood flow was estimated with 133Xe washout technique. The blood clearance rate constant of albures in non-activated rats was twice that for nanocoll (1.08 +/- 0.05 vs 0.49 +/- 0.02 10(-2)s-1). There was no mutual interaction between the two colloids, implying that they may be eliminated from the blood-stream by slightly different processes. In zymosan-stimulated animals, nanocoll given in a single injection showed a significantly increased k-value. Neither the albures clearance rate constant nor the nanocoll/albures k-value ratio revealed RES macrophage activation. By contrast the nanocoll/albures ratio, calculated for the liver, rose significantly. The final colloid uptake in the liver revealed RES macrophage activation. No changes in liver parenchyma blood flow per g tissue could be registered after administration of zymosan. The nanocoll and albures colloid particles did not impair the normal liver parenchyma blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins

Simulations of peritoneal solute transport during CAPD. Application of two-pore formalism.

Blood peritoneal clearances of various endogenous solutes in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were evaluated according to recent developments of the two-pore theory of membrane permeability, using a non-linear transport formalism for the analysis. Based on results obtained from these calculations and taking lymphatic drainage into account, transport from peritoneal cavity to the blood was also simulated. With respect to solute transport the data were compatible with a functional blood-peritoneal barrier consisting of a two-pore membrane containing a large number of paracellular "small pores" of radius 40 to 55 A and a small number of "large pores" of radius 200 to 300 A. Solutes smaller than 25 A in radius were found to be permeating across the peritoneal membrane mainly by means of diffusion across the small pores, whereas solutes larger than 40 A were calculated to reach the peritoneal cavity exclusively by unidirectional convection across the large pores. In addition, water was simulated to be transported through transcellular "ultrapores" (radius less than 8 A) not accessible to hydrophilic solute permeation. Small solute absorption from the peritoneal cavity was found to occur by diffusion across small pores. Molecules larger than 25 to 30 A in radius (molecular weight above 25,000) were simulated to be absorbed from the peritoneal cavity exclusively via non-size-selective lymphatic drainage.

Biological Transport

Pulmonary vascular permeability and resistance measurements in control and ANTU-injured dog lungs.

Because questions have arisen regarding pulmonary vascular permeability and resistance measurements in isolated, perfused lungs, we sought to determine the 1) stability of repeated measurements of permeability and resistance in control lungs; and 2) magnitude of change in these measurements when permeability was greatly increased. Using blood-perfused dog lungs, we measured filtration coefficient (Kf) and isogravimetric capillary pressure (Pci) as indexes of vascular permeability, and we also determined total vascular resistance (Rt) as well as the segmental resistances using the double-occlusion pressure (Pdo). In a control group (n = 8), the base-line measurement of Kf (0.21 +/- 0.02 ml.min-1.cmH2O-1.100 g-1) and Pci (10.2 +/- 0.9 cmH2O) did not change over 4 h, indicating no changes in endothelial barrier function. Base-line Rt (13.9 +/- 2.6 cmH2O.l-1.min.100 g) also did not significantly increase. In a second group (n = 5), alpha-naphthylthiourea (ANTU) increased the initial Kf more than eight times (from 0.17 +/- 0.03 to 1.40 +/- 0.32 ml.min-1.cmH2O-1.100 g-1) and decreased Pci by 56% (from 9.4 +/- 0.6 to 4.1 +/- 0.4 cmH2O) at 1 h, indicating severely damaged endothelium. In addition, the Pdo determined during isogravimetric conditions correlated very well with Pci not only in control lungs (observed previously) but also in very permeable lungs (not previously reported). We conclude that this experimental model provides an excellent means of assessing changes in pulmonary microvascular permeability, with a spectrum ranging from no changes in hourly measurements for 4 h to obvious changes in permeability by 1 h.

Animals

Oleic acid reduces pulmonary microvascular sieving capacity in sheep.

Changes in pulmonary microvascular permeability in sheep, after oleic acid injection, were studied using estimations of the osmotic reflection coefficient (sigma d) for total protein, albumin, immunoglobulins (Ig) G and M and calculation of the equivalent small and large pores of the microvessels. A chronic lung fistula was prepared in eight sheep. After a base-line period, left atrial pressure (Pla) was increased. Oleic acid (0.05 mg/kg body wt) was injected after a filtration-independent state had been obtained, and the spontaneously ventilating animals were then followed for 2 h. The sigma d for the normal lung was 0.65 +/- 0.03, 0.59 +/- 0.02, 0.72 +/- 0.04, and 0.84 +/- 0.02 for total protein, albumin, IgG, and IgM, respectively. The equivalent pore radii were 54 and 225 A. After oleic acid infusion, arterial pressure and arterial O2 tension decreased and leukocytes and platelets were consumed. At the end of the experiment, sigma d's were 0.27 +/- 0.04, 0.24 +/- 0.07, 0.33 +/- 0.06, and 0.55 +/- 0.04 for total protein, albumin, IgG, and IgM, respectively. The equivalent pore radii were 54 and 275 A, and the number of large pores was increased by 195%. The results indicate that oleic acid produces an increased vascular permeability by increasing the size and the numbers of large pores of the pulmonary microvascular walls.

Animals