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B Rippe

Publications and source records attributed to B Rippe.

At least 73 records · Page 4Linked to original sources

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↗

Transcapillary clearance of albumin in rat skeletal muscle monitored by external detection. Effects of alterations in capillary surface area.

The effects of noradrenaline (NA)-induced vasoconstriction on the transcapillary passage of albumin was evaluated by an external detection technique, allowing repetitive measurements of albumin clearance (Cl) during various conditions (in the same animal). Six isolated rat hindquarters were perfused with serum-albumin solutions during maximal vasodilation (papaverine 90 microM) and Cl was determined at different net filtration rates (Fv) induced by elevations of venous pressure. Then, the perfusate was changed to one of similar composition but containing noradrenaline (2-4 microM), and the procedure of determining Cl vs. Fv was repeated. Tissue accumulation of [99mTc]albumin was expressed in terms of clearance, using the isogravimetric Cl of defined muscle samples during maximum vasodilation in separate experiments as reference, the latter being 0.0246 +/- 0.0012 ml min-1 per 100 g. Noradrenaline caused an increase in vascular resistance from 2 to 14 mmHg min 100 g ml-1, while the Cl vs. Fv relationship was shifted downwards in a fashion parallel with the control Cl vs. Fv curve. For Fv = 0, Cl was 0.0101 +/- 0.0014 ml min-1 per 100 g during NA challenge. The average reflection coefficient for albumin (sigma tot) was 0.92 +/- 0.01 irrespective of vascular tone. Thus, both albumin clearance and the capillary filtration coefficient (CFC) seem to vary in direct proportion to the capillary surface area available for exchange.

Animals↗

Effects of oxygen free radical scavengers, xanthine oxidase inhibition and calcium entry-blockers on leakage of albumin after ischaemia. An experimental study in rabbit kidneys.

The effect of pretreatment with various substances protecting against oxygen free radicals on the leakage of proteins across the vessel walls of rabbit kidneys induced by ischaemia has been studied. The leakage of proteins was estimated from the difference between the 120-min distribution space of [131I]albumin and the 5-min distribution space of [125I]albumin, the latter mainly measuring the intravascular volume. Neither SOD (superoxide dismutase), catalase, allopurinol or two different Ca2+ channel blockers (nifedipine, felodipine) could alone reduce the leakage induced by ischaemia. A combined pretreatment with SOD, catalase and nifedipine reduced the leakage in the cortex, and pretreatment with mannitol alone reduced the leakage in the cortex and outer stripe of the medulla. The results indicate that oxygen free radicals are involved in the leakage of proteins across the vessel walls induced by ischaemia, but that other mechanisms are involved as well.

Allopurinol↗

Orosomucoid as one of the serum components contributing to normal capillary permselectivity in rat skeletal muscle.

The effects of human serum orosomucoid (normal serum concentration 0.7-1.0 g l-1) on capillary permeability were investigated in 12 isolated maximally vasodilated rat hindquarters perfused with bovine serum albumin (50 g l-1) in modified Tyrode. Measurements were made of capillary filtration coefficient (CFC), permeability surface area product (PS) for vitamin B12 and isogravimetric clearance of radiolabelled albumin (Cl alb). The results were compared with those obtained using perfusates without addition of orosomucoid ('albumin group') or perfusates containing horse serum ('serum group'). Clearance of albumin was almost four-fold higher in the albumin than in the serum group, 0.0895 +/- 0.0066 (n = 12) and 0.0252 +/- 0.016 ml min-1 per 100 g (n = 18), respectively, while intermediate Cl alb values were obtained with human orosomucoid in the perfusate (greater than 0.1 g l-1), 0.0436 +/- 0.0034 ml min-1 per 100 g) (n = 8). These changes in Cl alb were not accompanied by any differences in CFC or PS. We conclude that orosomucoid is one of the components in serum (besides albumin) needed for the maintenance of normal permselectivity of the capillary walls of rat skeletal muscle. Alternatively, human orosomucoid is structurally related to other substances exerting this 'serum effect'.

Animals↗

Influence of perfusate oncotic pressure on the transcapillary clearance of albumin in maximally vasodilated rat skeletal muscle.

An external detection technique was developed for repetitive and reliable measurements of clearance (Cl) of 99mTc-albumin during alterations of serum colloid osmotic pressure (pi p). Isolated, maximally vasodilated rat hindquarters were perfused with serum of two pi ps (20 mmHg and 45 mmHg) at four or five different filtration rates (Fv) for each pi p in each animal. The recorded accumulation rates of 99mTc-albumin (AR) were converted into dimensions of albumin clearance, setting the isogravimetric Cl at normal vascular pressures (pi p = 20 mmHg) at 0.0246 +/- 0.0012 ml min-1 per 100 g, which was obtained in defined muscle samples in 11 separate experiments. Serum perfusion with higher colloid osmotic pressure (45 mmHg) shifted the albumin clearance values upwards, without affecting the slope of the Cl vs. Fv relationship. Thus, the reflection coefficient (sigma) for albumin did not seem to be affected by the changes in pi p, while the isogravimetric albumin clearance was increased to roughly 0.058 ml min-1 per 100 g. Explicit two-pore equations were found to describe the experimental data fairly well, yielding an average sigma for albumin of 0.92 and a minor contribution of diffusion to overall transport even at low Fvs. Moreover, a coupling of macromolecular clearance to pi p may serve to minimize alterations in plasma protein concentration.

Animals↗