Osmotic Reflection Coefficient Research Articles

Osmotic reflection coefficient for total plasma protein in lung microvessels

The osmotic reflection coefficient (sigma) for total plasma proteins was estimated in 11 isolated blood-perfused canine lungs. Sigma's were determined by first measuring the capillary filtration coefficient (Kf,C in ml X min-1 X 100g-1 X cmH2O-1) using increased hydrostatic pressures and time 0 extrapolation of the slope of the weight gain curve. Kf,C averaged 0.19 +/- 0.05 (mean +/- SD) for 14 separate determinations in the 11 lungs. Following a Kf,C determination, the isogravimetric capillary pressure (Pc,i) was determined and averaged 9.9 +/- 0.5 cmH2O for all controls reported in this study. Then the blood colloids in the perfusate were either diluted or concentrated. The lung either gained or lost weight, respectively, and an initial slope of the weight gain curve (delta W/delta t)0 was estimated. The change in plasma protein colloid osmotic pressure (delta IIP) was measured using a membrane osmometer. The measured delta IIP was related to the effective colloid osmotic pressure (delta IIM) by delta IIM = (delta W/delta t)0/Kf,C = sigma delta IIP. Using this relationship, sigma averaged 0.65 +/- 0.06, and the least-squares linear regression equation relating Pc,i and the measured IIP was Pc,i = -3.1 + 0.67 IIP. The mean estimate of sigma (0.65) for total plasma proteins is similar to that reported for dog lung using lymphatic protein flux analyses, although lower than estimates made in skeletal muscle using the present methods (approximately 0.95).

Permselectivity of the peritoneal membrane

To investigate the osmotic barrier characteristics of the peritoneal membrane during conditions similar to peritoneal dialysis in man, net transperitoneal fluid movement was measured in 20 cats following intraabdominal placement of isotonic saline and hypertonic solutions of NaCl, glucose, raffinose, and inulin. Also, isooncotic solutions of hemoglobin and albumin and two sulfated high-molecular-weight dextrans were investigated. Transperitoneal fluid movement was measured by a volume recovery method. Oncotic pressures of test solutions and plasma were measured by osmometry. Peritoneal osmotic conductances were calculated from the rate of transperitoneal water movement and the difference in osmotic pressures between the test solution and isotonic saline. The average glucose osmotic conductance per unit body surface area was found to be 2.3 ± 0.18 × 10 −3 ml · min −1 · mm Hg −1 · m −2, in good agreement with previous reports, and the glucose osmotic reflection coefficient (σ) was estimated to be 0.02. All the osmotic conductances measured could be fitted to a peritoneal equivalent pore radius of approximately 6 nm according to current hydrodynamic theories. The peritoneal membrane filtration coefficient was estimated to be 0.12 ml · min −1 · mm Hg −1 · m −2, of which 0.5–1% was found to be due to transcellular water flow. In conclusion the results of this study indicate that the peritoneum is a highly selective membrane with restrictive properties comparable to those reported for continuous capillary beds.

Role of the microcirculation in ethanolinduced mucosal injury in the dog

The aim of the present study was to assess the role of the intestinal microcirculation in the mucosal injury induced by intraenteric ethanol. Mucosal injury was assessed histologically in the ileum and jejunum and quantitated in the ileum by measuring clearance of albumin (37 Å, radius) and β-lactoglobulin A (27 Å, radius). A steady-state analysis of the forces and flows governing transcapillary fluid movement was performed in autoperfused segments of jejunum and ileum. In the jejunum and ileum ethanol induced the formation of subepithelial blisters in 10%–40% of the villi. In the ileum, ethanol (5%, vol/ vol) increased the clearance of both proteins but the ratio of lactoglobulin to albumin clearance decreased, indicating that the selectivity of the mucosal membrane was diminished. In both the jejunum and ileum ethanol produced similar alterations in the forces governing transcapillary fluid exchange. Ethanol increased the filtration coefficient (35%–40%), but did not alter the osmotic reflection coefficient of intestinal capillaries, indicating that surface area increased whereas vascular permeability was not affected. Capillary pressure increased (2–3 mmHg) whereas interstitial (lymph) protein concentration decreased resulting in an increase in the transcapillary oncotic pressure gradient (1–2 mmHg). The net result of the alterations in the forces governing transcapillary movement was only a doubling of the transcapillary filtration rate (lymph flow). It is concluded that the ethanol-induced increase in mucosal permeability to macromolecules cannot be explained solely on the basis of alterations in the forces and flows governing transcapillary fluid exchange in the small intestine.

Effect of neurotensin on intestinal capillary permeability and blood flow

Experiments were performed in 10 cats of either sex to ascertain the effects of postprandial arterial plasma concentrations of neurotensin (NT) on intestinal capillary permeability and blood flow. NT was infused intra-arterially into an isolated perfused loop of terminal ileum to produce a 182 +/- 15 (SE) pM plasma NT concentration. Intestinal lymph (L) and plasma (P) protein concentrations were measured at various venous pressures under control conditions and during NT infusion. The osmotic reflection coefficient (sigma d) was estimated under all conditions assuming sigma d = 1 - L/P at high capillary filtration rates. NT infusion significantly (P less than 0.001) reduced sigma d to 0.73 +/- 0.02 (SE) from a control level of 0.91 +/- 0.01. NT infusion also significantly increased intestinal blood flow [47.0 +/- 4.3 (SE) ml X min-1 X 100 g-1] versus control (36.6 +/- 3.2 ml X min-1 X 100 g-1), a 28.4% increase. Intestinal vascular resistance was decreased from 3.21 +/- 0.31 to 2.42 +/- 0.28 mmHg X min X ml-1 X 100 g in the absence of a change in local mean arterial blood pressure. Pore-stripping analysis of lymph and plasma solute fractions during NT infusion at high lymph flows predicted two populations of pores, 330-A and 46-A radius, accounting for 31 and 67%, respectively, of the total transcapillary hydraulic flow. NT infusion preferentially increased large-pore radius as a means of increasing intestinal capillary permeability. The rates of small- to large-pore areas and numbers were 106:1 and 5,225:1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen radicals: effects on intestinal vascular permeability.

There is now a considerable amount of evidence in the literature implicating oxygen-derived free radicals in the vascular permeability changes associated with intestinal ischemia. To directly assess the effects of oxygen radicals on vascular permeability, hypoxanthine-xanthine oxidase, an enzyme-substrate system known to generate oxygen free radicals, was infused into the arterial supply of autoperfused segments of cat ileum. The osmotic reflection coefficient (sigma d) of intestinal capillaries to total plasma proteins was estimated from the steady-state relationship between lymph-to-plasma total protein concentration ratio and lymph flow. Intra-arterial infusion of hypoxanthine-xanthine oxidase reduced sigma d from a control value of 0.92 to 0.66, indicating an increased vascular permeability. This increase in vascular permeability was significantly attenuated by the addition of superoxide dismutase (sigma d = 0.86), a specific scavenger of superoxide anion (O2-), or dimethylsulfoxide (sigma d = 0.83), the hydroxyl radical (OH X) scavenger, to the infusate. The results of this study indicate that oxygen-derived free radicals, generated by the reaction of hypoxanthine with xanthine oxidase, increase intestinal vascular permeability to an extent comparable with that observed in preparations subjected to 1 h of ischemia.

Assessment of pulmonary microvascular permeability in acutely prepared sheep.

We hypothesized that the apparent difference in base-line lymph-to-plasma protein concentration ratios (L/P) between acutely and chronically prepared sheep is due to an underlying difference in pulmonary microvascular permeability. Therefore, we sought to determine the pulmonary microvascular osmotic reflection coefficient for acutely prepared sheep, in a manner similar to that used by Parker et al. (Circ. Res. 49: 1164-1172, 1981) in chronically prepared animals. In 20 acutely prepared sheep, we evaluated pulmonary lymph flow (QL) and L/P as left atrial pressure was progressively elevated. As a result of the elevated hydrostatic pressure, QL increased by 28 to 773% above base-line flows, accompanied by substantial dilution of lymphatic protein. At high QL, L/P approached a minimal value, (L/P)min, of 0.39. The osmotic reflection coefficient (sigma d), calculated as sigma d = 1 - (L/P)min, was 0.61, substantially lower than the value of 0.74 found by Parker et al. in chronically prepared sheep. We conclude that the higher base-line L/P found in acutely prepared sheep is due to higher pulmonary microvascular permeability, possibly the result of the more immediate surgical trauma.

Failure of myocardial ischemia to increase pulmonary microvascular permeability in dogs.

Increased extravascular lung water has been reported following periods of myocardial ischemia. To determine whether increased pulmonary microvascular permeability was produced by ischemia, total protein lymph-to-plasma concentration ratios (CL/CP) were obtained at mechanically increased left atrial pressures (Pla) before and after ligation of the left anterior descending coronary artery in dogs. Pulmonary and systemic vascular pressures and cardiac output were monitored and lymph flow was measured from an afferent tracheobronchial lymphatic. Osmotic reflection coefficients (sigma) for total protein were estimated using CL/CP = 1-sigma at high filtration rates, and permeability-surface area (PSf) products were fit to the data. The postischemic lung lymph data best fit average values of sigma = 0.68 and PSf = 0.073 ml X min-1 X 100 g-1 wet weight. There were no significant differences in lymph protein or water clearances between the pre- and postischemic increased Pla states or for myocardial ischemia compared with control values for the experimental preparation. Levels of 6-ketoprostaglandin F1 alpha, a degradation product of prostacyclin, increased by 10- to 14-fold above preischemic values in pulmonary lymph, and there was a significant increase in pulmonary vascular resistance during ischemia. Extravascular lung water was not increased above that attributed to the increased Pla alone. These data indicate no significant increase in pulmonary microvascular permeability to plasma proteins during myocardial ischemia.

Acute local effects of angiotensin II on the intestinal vasculature.

The vasotoxic properties of angiotensin II (AII) on vascular endothelial cells have been implicated in the increased extravasation of proteins and water observed in certain forms of chronic arterial hypertension. Since microvascular permeability in the small intestine is increased in one-kidney, one clip hypertension, we tested the hypothesis that AII decreases the permselectivity of intestinal microvessels to plasma proteins. The acute intestinal vascular effects of AII were studied by locally infusing AII into isolated canine jejunal segments. A measure of vascular permeability in control and infused segments was obtained by estimating the osmotic reflection coefficient as 1-lymph/plasma protein concentration ratio when the ratio reached a plateau at high lymph flows. Lymph flows were increased by raising the venous pressure from a control of 5 to 30-35 mm Hg in 5 mm Hg steps. Resting control blood and lymph flows were reduced by AII, but these flows were not different at the higher venous pressures due to the apparent blunting of the venous-arteriolar response by AII. The estimated osmotic reflection coefficient of 0.85 for the control animals was less than that obtained in the infused segments (0.93). This effect was substantiated by electrophoretic separation of protein fractions. Thus, AII per se does not cause an acute increase in intestinal vascular permeability, and may, in fact reduce it.

Solute concentration effect on osmotic reflection coefficient

A theory for the effect of concentration on osmotic reflection coefficient, correct to first order, was developed at the molecular level by considering the effect of solute-solute interactions on solute concentration and the fluid stress tensor within a solvent-filled pore. The solvent was modeled as a continuous fluid and potential energies between solute molecules and the pore wall were assumed to be pairwise additive. Although the theory is more general, calculations are presented only for excluded volume effects (hard-sphere for solute, hard-wall for pore). The relationship between the first-order concentration effect and the infinite dilution value of reflection coefficient appears to be geometry independent. The theory is discussed in light of experimental studies of osmotic flow that have recently appeared in the literature.

Restricted transport of cationic macromolecules across intestinal capillaries.

The charge-selective properties of intestinal capillaries were investigated by measuring steady-state lymph-to-plasma concentration ratios (L/P) of endogenous and exogenous macromolecules of comparable molecular size but different charge. The steady-state L/P values for endogenous lactate dehydrogenase isoenzymes (LD1-LD5) decreased with increasing isoelectric point. The osmotic reflection coefficient for LD1, the most negative isoenzyme studied, was 0.71 +/- 0.01; that for the most positive isoenzyme (LD5) was 0.95 +/- 0.01. The steady-state L/P for an exogenous molecule, neutral dextran, was 0.51 +/- 0.04; the L/P for the positively charged dextran of similar size was 0.25 +/- 0.04. The results indicate that intestinal capillaries behave as a positively charged barrier that reduces blood-lymph exchange of cationic macromolecules and enhances the exchange of anionic molecules.

Ischemia-induced vascular changes: role of xanthine oxidase and hydroxyl radicals.

The results of previous studies indicate that oxygen-derived free radicals are responsible for the increased vascular permeability produced by 1 h of intestinal ischemia. The aims of this study were 1) to test the hypothesis that the enzyme xanthine oxidase is the source of oxygen radicals in the ischemic bowel and 2) to assess the role of the hydroxyl radical in the ischemia-induced vascular injury. The capillary osmotic reflection coefficient was estimated from lymphatic protein flux data in the cat ileum for the following conditions: ischemia, ischemia plus pretreatment with allopurinol (a xanthine oxidase inhibitor), and ischemia plus pretreatment with dimethyl sulfoxide (a hydroxyl radical scavenger). The increased vascular permeability produced by ischemia was largely prevented by pretreatment with either allopurinol or dimethyl sulfoxide. These findings support the hypothesis that xanthine oxidase is the source of oxygen radicals produced during ischemia. The results also indicate that hydroxyl radicals, derived from the superoxide anion, are primarily responsible for the vascular injury associated with intestinal ischemia.

Microcirculation of the alimentary tract: I. Physiology of transcapillary fluid and solute exchange

Introduction Anatomic Considerations Capillaries Salivary glands Pancreas Stomach Small intestine Colon Pathways for transcapillary exchange Interstitium Lymphatics Stomach Small intestine Colon Salivary glands Pancreas Physiology of Capillary Fluid and Solute Exchange Capillary Fluid Exchange Lymph flow Capillary filtration coefficient Capillary pressure Interstitial fluid pressure Osmotic reflection coefficient Oncotic pressure gradient Interactions of Capillary and Interstitial Forces Enhanced capillary filtration-edema safety factors Reduced capillary filtration-safety factors against interstitial dehydration Net transepithelial fluid transport Secretion Absorption Filtration secretion

Increased pulmonary microvasuclar permeability induced by alpha-naphthylthiourea

The effects of alpha-naphthylthiourea (ANTU) on lung microvascular permeability to plasma proteins were studied in anesthetized open-chest dogs. Lymph flow (Jv) was recorded, and total protein in plasma and lymph was analyzed after cannulating a small prenodal lung lymphatic. The protocol involved four experimental periods. Period 1. During this base-line period the preparation stabilized and steady states were reached in Jv, lymph total protein, pulmonary arterial pressure (Ppa), and left atrial pressure (Pla). Period 2. Pla was increased to approximately 20 cmH2O and maintained at that level until Jv and protein measurements attained a new steady state. Period 3. After Pla was lowered to control levels, ANTU (5 mg/kg body wt) was infused intravenously and parameters were measured for 3 h. Period 4 Pla was again raised to the pre-ANTU levels of period 2 and maintained for an additional 2-3 h. The lymphatic total protein clearance increased 8.6-fold for an equivalent increase in pulmonary capillary pressure after ANTU. Vascular permeability was assessed by estimating the osmotic reflection coefficient (sigma d) for total protein at the pulmonary capillary membrane. Sigma d decreased from 0.65 to 0.40 following ANTU. From plasma protein fractions in four experiments, equivalent pore radii for the capillary membrane of 95 and 280 A were calculated after ANTU compared with 80 and 200 A for normal lung capillaries. In addition, extravascular lung water increased from 3.8 +/- 0.16 to 5.87 +/- 0.25 following ANTU and to 7.55 +/- 0.55 (g/g blood-free dry wt) when Pla was elevated with ANTU. The experimental design allowed quantitative assessment of the vascular permeability increase after ANTU by use of lymph protein fluxes that had minimal errors due to changes in surface area or lymph contamination from nonpulmonary structures.

Permeability of intestinal capillaries: effects of fat absorption and gastrointestinal hormones.

The purpose of this study was to determine whether the postprandial increase of intestinal lymphatic protein flux is due to an increased capillary permeability. Intestinal lymph flow and lymph (L) and plasma (P) protein concentrations were measured at various venous pressures under control conditions, after cream feeding, and during intraluminal perfusion with a bile-oleic acid solution. The osmotic reflection coefficient (sigma d), a measure of capillary permeability that is independent of surface area, was estimated under all conditions, assuming sigma d = 1 - L/P at high capillary filtration rates. The results acquired indicate that cream feeding and intraluminal perfusion with bile-oleic acid significantly increases intestinal capillary permeability. Pretreatment with indomethacin and antihistamines did not alter the permeability increase induced by intraluminal bile-oleic acid. Intra-arterial infusion of cholecystokinin and secretin did not increase intestinal capillary permeability. These studies indicate that the postprandial increase in intestinal lymphatic protein flux is due at least in part, to an increase in capillary permeability. Cholecystokinin, secretin, histamine, and prostaglandins do not appear to mediate the increased intestinal capillary permeability during fat absorption.

Estimation of whole-body capillary transport parameters from osmotic transient data.

A mathematical model has been developed of short-term, extrarenal, whole-body fluid volume regulation. The Kedem and Katchalsky equations are used to describe rapid movements of crystalloid and colloid solutes and water between five fluid compartments. Simulation results showing rapid cell volume changes following a hyperosmotic crystalloid infusion demonstrated the necessity of considering the effect of cellular water shifts in osmotic transient experiments. From measurements of plasma volume and osmolality in acutely nephrectomized dogs subjected to isosmotic and hyperosmotic NaCl infusions and with the model, six parameters related to capillary membrane transport of water and NaCl were estimated. The mean capillary filtration capacity from six experiments was estimated as 0.01 ml.min-1.mmHg-1.100 g-1 of dog. This increased about threefold due to the hyperosmolality. Mean values of capillary diffusion capacity and osmotic reflection coefficient for NaCl were 0.37 cm3.s-1.100 g-1 and 0.087, respectively. These results support the use of the osmotic transient approach and a mathematical model to study the role of microvascular transport in whole-body fluid volume regulation.

Permeability of gastric capillaries to small and large molecules.

The permeability of capillaries in the stomach to small and large solutes was studied with the double-indicator diffusion technique in the dog stomach and by analysis of steady-state lymph and plasma samples in the cat stomach. The effective pore radius in gastric capillaries determined by indicator diffusion was 53 A, whereas steady-state lymph samples predicted a small-pore radius of 47 A. At the highest plasma flow rates studied (achieved by intra-arterial infusion of isoproterenol), indicator diffusion estimates of the permeability-surface area product for raffinose, inulin, and beta-lactoglobulin A were 140, 70, and 8 ml . min-1 . 100 g-1, respectively. The lymph studies indicate that gastric capillaries are more permeable than capillaries in the intestine and colon to albumin and larger molecules. The calculated effective large-pore radius of gastric capillaries was 250 A. The osmotic reflection coefficients (sigma d) ranged from 0.73 +/- 0.03 for albumin to 0.91 +/- 0.02 for beta-lipoprotein (120-A radius). The sigma d for total plasma protein was 0.78 +/- 0.03, indicating a substantial transcapillary oncotic pressure gradient, despite the greater permeability of these capillaries for macromolecules.

Electrolyte osmosis through capillaries

Electrolyte-osmosis through porous membranes is investigated using the capillary model for the membrane. The electrical double layers which form because of the charge on the walls of the pore, together with the concentration gradient of the electrolyte across the pore, generate the driving forces responsible for osmosis. The basic equations that govern the flow of electrolyte solution through the pore (i.e., momentum, convective-diffusion, and Poisson-Boltzmann equations) are solved numerically to relate the characteristics of the osmotic flow (solute and solvent fluxes, osmotic reflection coefficient, and hydraulic permeability coefficient) to the characteristics of the pores (surface charge, radius, and length) and to the concentrations c I and c II of the bulk solutions on both sides of the membrane. The effect of the electric field and the radial dependence of electrical potential, concentration, and pressure inside the pores are taken into account in the analysis. The effect of an imposed pressure gradient between the two reservoirs, acting in the same direction as the concentration gradient, is examined to establish the domains of osmosis and reverse osmosis. The role of a pressure gradient applied against the concentration gradient is also considered. The influence of the unequal diffusion coefficients for anions and cations (diffusional potential) on the osmotically driven flows is studied by comparing the osmotic flow velocity of KCI solutions with those of KBrO 3 and NaCl. Lastly, the effect of an impermeable nonionic solute, added to the salt solutions on the osmotic flow rate and electrolyte flux, is evaluated. The paper provides a unified treatment for osmosis and reverse osmosis.

Intracapillary events in osmotic weight transients

In osmotic transient experiments on perfused organs the time course of the concentrations of both test and resident buffer solutes within the capillary must be known in order to give an adequate description of the underlying events leading to the observed weight changes. In accompanying papers ( G. Bloom and J. A. Johnson, 1981, Microvasc. Res. 22, 64–79, J. A. Johnson and G. Bloom, 1981, Microvasc. Res. 22, 80–92), we describe a model for osmotic transients based on the assumption that both test and buffer solute concentrations within the capillary are constant. In this paper we determine the magnitude and time course of solute concentration changes within the capillary and show the effect of inserting these values into our model in place of the previously assumed constant concentrations. In particular we show what effect these changes in solute concentration have on our estimates of capillary osmotic reflection coefficients (σ) and permeability coefficients ( P) for inulin and sodium chloride. A mathematical analysis is presented which describes the concentration as a function of time as the new solution moves through the following segments of the fluid pathway preceding the heart capillaries: (1) the tubing conduits to the heart; (2) the mixing chamber of the aortic bulb; (3) the precapillary vascular system. This analysis is combined with that of J. A. Johnson and T. A. Wilson (1966, Amer. J. Physiol. 210, 1299–1303) on the axial profile of capillary concentration caused by solute movement across the capillary wall. A mathematical analysis of the intracapillary buffering which could arise due to sieving of resident solute at the capillary wall is presented in an appendix. We find that perfusion rates similar to those that we employ in our experimental system enable us to obtain valid estimates of PA and σ. Significantly lower perfusion rates do not yield valid results.

Effects of histamine and histamine antagonists on intestinal capillary permeability.

Steady-state lymph flow, blood flow, and lymph and plasma total protein concentration were measured in an autoperfused cat ileum preparation during the continuous infusion of histamine at venous pressures of 0, 10, 20, and 30 mmHg. The capillary osmotic reflection coefficients for total proteins and each protein fraction were estimated. In addition, the ileum was pretreated with an H1-receptor antagonist (diphenhydramine) or with an H2-receptor antagonist (cimetidine). The results suggest that histamine selectively increases the ileal vascular permeability to plasma proteins of a molecular radius up to 96 A. The H1-receptor antagonist did not alter the histamine-induced permeability changes but did block the observed initial vasodilation. The H2-receptor antagonist significantly reduced the permeability changes associated with histamine while having only a slight effect on the initial vasodilation. It is concluded that the activation of H1-receptors is predominantly associated with the initial vasodilation, whereas the H2-receptors are predominantly associated with permeability.

Vascular permeability and transvascular fluid and protein transport in the dog lung.

We used steady state lymph-to-plasma concentration ratios of six endogenous protein fractions (effective hydrodynamic radii of 37, 40, 44, 53, 100, and 120 A) to estimate pulmonary capillary permeability characteristics. Pulmonary lymph was collected from an afferent lymphatic to the left tracheobronchial lymph node, and left atrial pressure was elevated in steps until the lymphatic protein concentration obtained a constant value. Lymph flow and transvascular protein flux increased with each increase in left atrial pressure. Convective flux was the predominant mode of transport for the smaller fractions, and solvent-drag reflection coefficients increased as lymph flow increased. This dependency on lymph flow (capillary filtration) indicates a heteroporous membrane system. For lymph flows greater than five times control, the solvent-drag reflection coefficients were: 0.59 +/- 0.11, 0.52 +/- 0.06, 0.66 +/- 0.05, 0.70 +/- 0.05, 1.01 +/- 0.04, and 1.05 +/- 0.03 for the six fractions. Osmotic reflection coefficients estimated from the minimal lymph-to-plasma concentration ratios were: 0.50 +/- 0.03, 0.59 +/- 0.02, 0.67 +/- 0.04, 0.72 +/- 0.03, 0.94 +/- 0.01, and 0.96 +/- 0.01 for the six protein fractions. The osmotic reflection coefficients are consistent with a two- "pore" exchange model possessing equivalent pore radii of 80 and 200 A. Theoretical considerations indicate that only the two largest protein fractions (100 A and 120 A radii) achieved filtration-independent concentrations in pulmonary lymph, even at the highest filtration rates. This suggests that the reported osmotic reflection coefficients of the four small protein fractions underestimate their true values.