Biomedical subjects

R K Reed

Publications and source records attributed to R K Reed.

At least 73 records · Page 4Linked to original sources

PubMed1994

Neurogenic inflammation and lowering of interstitial fluid pressure in rat trachea is inhibited by alpha-trinositol.

The effect of alpha-trinositol (D-myoinositol-1,2,6-triphosphate) on edema formation and capillary permeability in neurogenically induced inflammatory edema was investigated in rat trachea. Interstitial fluid pressure (Pif) was studied, since increased negativity of Pif contributes to edema formation in this situation. alpha-Trinositol was used because it inhibits edema formation, capillary leakage, and increased negativity of Pif in burn-injured skin. Pif was measured with sharpened glass capillaries (3 to 7 microns) connected to a servocontrolled counterpressure system after circulatory arrest (induced by intracardiac injection of saturated potassium chloride in pentobarbital anesthesia). This was done in order to avoid the edema formation associated with inflammatory reactions, which will raise interstitial fluid volume and Pif, causing the underestimation of an increased negativity of Pif. Neurogenic inflammation induced by electrical-field stimulation of the left vagal nerve (10 V, 20 Hz, 0.5 ms) lowered Pif from -1.4 +/- 0.6 mm Hg to -8.4 +/- 2.1 mm Hg (p < 0.01). Corresponding numbers after the intravenous administration of alpha-trinositol (40 mg/kg) before stimulation were -1.2 +/- 0.4 and -1.4 +/- 0.4 mm Hg, respectively (p > 0.05). Another series of animals with intact circulation was used to study the effect of vagal nerve stimulation and alpha-trinositol on edema formation (total tissue water and extravascular 51Cr-ethylenediamine tetraacetic acid-[EDTA] space) and albumin extravasation. These parameters increased significantly after vagal nerve stimulation, while intravenous alpha-trinositol (40 and 120 mg/kg), as given above, significantly attenuated this increase. Thus, alpha-trinositol prevented a lowering of Pif and the edema formation accompanying neurogenic inflammation in rat trachea.

Analysis of Variance↗

PubMed1994

Hyaluronan efflux from canine lung with increased hydrostatic pressure and saline loading.

Although lymphatic washout of hyaluronan during lung hydration has been postulated to deplete lung interstitial hyaluronan content and thereby contribute to the decreased interstitial exclusion of albumin observed under these conditions, this hypothesis has not been directly tested. In anesthetized, ventilated mongrel dogs, a prenodal lung lymphatic was cannulated for measurement of lymph flow and hyaluronan concentration. Following baseline measurements, Pla was increased in four steps of 5 cm H2O in Group 1 or set to one pressure ranging between 6 and 32 cm H2O in Group 2. In Group 3, saline (15% body weight) was infused over 30 min and then Pla increased as in Group 2. Invariably, as lymph flow increased in Groups 1 through 3, lymph hyaluronan concentration and hyaluronan flux increased significantly (p < 0.05). In a separate control group, there were no changes in lymph flow, hyaluronan concentration, or hyaluronan flux. In Group 3, lung hyaluronan content at 5 h (0.76 +/- 0.08 mg/g dry weight) was not significantly less than that during baseline (0.88 +/- 0.05 mg/g dry weight), although total uronic acid content actually increased by 38% over the same time course. In contrast, in the control group, both lung hyaluronan and uronic acid content remained stable over the experimental period. From these data, approximately 2 to 3% of lung hyaluronan is predicted to leave the interstitium via lymphatic flux per day under baseline conditions. The daily turnover of interstitial hyaluronan by this route increased to 15 to 18% of total content when Pla was elevated and to 54% following saline infusion. Thus, lung hyaluronan can be rapidly mobilized with increased lymph flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

[Anders Jahre-Award for young researchers 1993. Loose connective tissue and fluid balance. From static to dynamic tissue].

Rolf K Reed, recipient of the 1993 Anders Jahre Prize for younger medical researchers, describes some newer aspects of loose (areolar) connective tissue physiology and shows how research in recent years has changed our understanding of the involvement of these tissues in the regulation of fluid balance. There is a dynamic relationship between loose connective tissue and fluid balance, as a result of which the development of oedema is normally inhibited. However, certain inflammatory reactions are accompanied by changes in the activity of these tissues which then "absorb" fluid from the capillaries. This feature seems to be partly related to hyaluronidase+, the metabolism of which is also dependent on connective tissue fluid balance.

Awards and Prizes↗

PubMed1993

Increased negatively of interstitial fluid pressure in rat skin contributes to the edema formation induced by Zymosan.

Increased negatively of interstitial fluid pressure (Pif) contributes to rapid edema formation in several acute inflammatory reactions attesting to an "active" role for the loose connective tissues in the transcapillary fluid exchange and edema formation under these circumstances. The present study reports the effect of the complement activator Zymosan on Pif, transcapillary fluid, and albumin flux. Micropipettes (tip diameter 5 to 7 microns) connected to a servo-controlled counterpressure system were used to measure Pif in rat dermis. When compared to saline injection, subdermal injection of 1 mg Zymosan in 10 microliters 0.15 M NaCl increased total tissue water by 1.6 ml/g dry weight in 5 min, corresponding to about 150% increase in interstitial fluid volume. Pif increased from +0.4 to +3.7 mm Hg. Increased negativity of Pif can be masked by the edema formation which will increase Pif. Measurements were therefore also performed after circulatory arrest, when transcapillary fluid flux and edema formation are abolished. Using this experimental protocol Pif fell from +0.3 mm Hg to -2.5 mm Hg 5 min after subdermal injection of Zymosan and remained at this level throughout the observation period of 90 min. Injection of saline alone after circulatory arrest increased Pif transiently by about 1 mm Hg. Thus, subdermal injection of Zymosan causes increased negativity of Pif by about 4 mm Hg. Although the lowering of Pif itself will explain a minor part of the increased fluid filtration, the results attest to the role of loose connective tissues being active in the edema-generating process also in the inflammatory reaction induced by Zymosan.

Animals↗

PubMed1993

A model of human microvascular exchange: parameter estimation based on normals and nephrotics.

A mathematical model is formulated and used to describe the distribution and transport of fluid and albumin in the human circulation, interstitium and lymphatics. Two transcapillary mass exchange mechanisms are investigated: a homoporous 'coupled Starling model', in which transcapillary albumin diffusion and convection occur within the same pathway, and a heteroporous 'plasma leak model', in which variations in structure and pressure are permitted along the length of the capillary. Parameters used in the transport models are determined based on statistical fitting of simulation predictions to experimental data from normal humans and nephrotic patients. The data consists of interstitial fluid volumes and interstitial colloid osmotic pressures as functions of plasma colloid osmotic pressure. Model validation is carried out based on comparison of (i) simulation predictions with experimental data used in parameter estimation, (ii) estimated transport parameters with experimentally determined values, and (iii) simulation predictions with a set of dynamic data from an albumin infusion study. While both models with their best-fit parameter estimates provide a good representation of experimental data, the drawbacks of the plasma leak model are three-fold: it requires more estimated parameters than the coupled Starling model, little experimental information exists with which to compare these parameters and, with the best fit values obtained, the plasma leak mechanism becomes insignificant. The model that employs a Starling-type exchange mechanism will therefore be favoured in future applications.

Arteries↗

PubMed1993

Vasostatins, comprising the N-terminal domain of chromogranin A, suppress tension in isolated human blood vessel segments.

Chromogranin A (CGA) belongs to a family of highly acidic proteins which are co-stored and co-released with the catecholamines from the mammalian adrenal gland and occur in nmolar concentrations in the human circulation. A vascular function for the adrenomedullary released and circulating CGA has yet to be established. The present study reports on the novel vasoinhibitory effect of the N-terminal domain of the adrenomedullary CGA in isolated segments of the human internal thoracic artery (ITA) and saphenous vein (SV). The collective term vasostatin(s) refers to N-terminal fragments (CGA1-76 and CGA1-113) of apparent molecular weights 7 to 22 kD, to indicate their vascular inhibitory effects. The sustained contractions evoked by the potent vasoconstrictor peptide, endothelin-1 (ET-1) were suppressed when ITA and SV segments were preincubated for 15 min with vasostatins (72 nM). The vasoinhibitory effects were not dependent on an intact endothelium and suppression of the response to 35 nM ET-1 was approximately 77% and approximately 40% in endothelium-denuded ITA and SV segments, respectively. In endothelium-denuded SV segments the vasostatins suppressed the maximal sustained tension response but not the potency for ET-1, indicating that the vasostatin effect did not involve interference with ET-1 binding to its vascular receptor. Preincubation of endothelium-denuded SV segments with nifedipine (1 microM) inhibited the sustained response to ET-1 > or = 10 nM by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Intravenous saline infusion in rat increases hyaluronan efflux in intestinal lymph by increasing lymph flow.

The output of hyaluronan in mesenteric lymph was studied in anaesthetized rats to allow estimation of the turnover rate. The duodenum/jejunum contained 45 micrograms of this glycosaminoglycan per g wet tissue weight. In fasted rats the concentration of hyaluronan in postnodal lymph averaged 15 micrograms ml-1 and the mean efflux was 2.1 micrograms h-1, corresponding to a daily removal of 10% of the intestinal hyaluronan content. An intravenously injected bolus of 0.9% saline 4 ml 100 g-1 followed by an infusion of the same amount per hour increased the hyaluronan concentration in lymph transiently to 22 micrograms ml-1. During the 8-h i.v. infusion the hyaluronan output remained five times above control due to the high lymph flow. Water and hyaluronan content of the small intestine remained unaltered despite the saline load, the maintained tissue level of hyaluronan suggests an increased rate of synthesis.

Animals↗

PubMed1993

Hyaluronan turnover in the rat small intestine.

The main metabolic pathway for the interstitial matrix component hyaluronan seems to be via lymph. Present estimates of turnover of intestinal hyaluronan are based on isolated organs and/or experiments in anaesthesia over a few hours. In this study lymph was sampled from the main mesenteric lymphatic for 24 h in awake, restrained rats. The tissue content of hyaluronan averaged 28 micrograms g-1 in the duodenum/jejunum and 124 micrograms g-1 in the colon. Based on tissue content and lymphatic output, the turnover rate of hyaluronan in the small intestine was estimated at approximately 50%. In another experimental group anaesthetized rats were fed either phosphate buffer or triolein in buffer via a gastric tube. Lymph flow increased with fluid absorption from the gut and hyaluronan output in lymph was elevated correspondingly. However, no effect of acute fat administration on hyaluronan concentration or lymph flow could be demonstrated.

Animals↗

PubMed1993

Blood-to-tissue clearance vs. lymph analysis in determining capillary transport characteristics for albumin in skin.

The blood-to-tissue clearance of radioactive albumin and a lymphatic flux analysis were used to evaluate the transport properties of albumin in the canine hindpaw. A prenodal lymphatic was cannulated, and lymph was collected for a 2-h control period. Thereafter venous pressure was elevated between 7 and 31 mmHg. After 2 h of increased venous pressure, the radioactive tracer was given intravenously. During the next 2 h lymph was sampled, and at the end of this time tissue and blood samples were obtained. The experiments showed that, of the tracer filtered in excess of control at increased venous pressure, an estimated 21% was cleared via the lymphatics and 79% was retained in the tissue. As a percentage of total tracer flux at increased venous pressure, 9% (measured) was drained by lymph and 91% was retained in the tissue. Of the fluid filtered in excess of control at increased capillary pressure, 70% (measured) was drained via the lymphatics and 30% was retained in the tissue in the same period. Twice the amount of endogenous albumin filtered across the capillary wall was drained via the lymphatics during the experimental period. The lymphatic washout of endogenous albumin from the interstitium will cause an underestimation of the capillary reflection coefficient and overestimation of the permeability-surface area product. Because of the loss of tracer from the tissue, the opposite occurs when the blood-to-tissue clearance of radioactive albumin is used.

Animals↗

PubMed1993

Increased negativity of interstitial fluid pressure in rat trachea after mast cell degranulation.

The present study was performed to investigate whether the increased negativity of interstitial fluid pressure (Pif) observed after intravenous injection of dextran could be mediated via mast cell degranulation induced by C48/80 and polymyxin B sulfate. Increased negativity of Pif, concomitant with edema formation and increased albumin extravasation, was seen with both substances. However, the two substances differed in that polymyxin B sulfate induced less negativity in Pif and a larger but transient increase in capillary albumin extravasation and interstitial fluid volume. Total tissue water (TTW) increased from 2.11 to 2.71 ml/g dry wt 10 min after polymyxin B and returned to control level at 30 and 60 min. Injection of C48/80 increased TTW to 2.68 ml/g dry wt at 30 min, and TTW was still elevated at 60 min. Albumin extravasation followed a similar pattern; polymyxin B sulfate increased albumin extravasation from < 0.08 to 1.18 ml/g dry wt during the first 5 min after administration. C48/80 was less potent, and maximal albumin leakage was seen after 10-25 min (0.25 ml/g dry wt). The observations demonstrate the importance of the interstitium and the loose connective tissues as "active" participants in the edema-generating process and suggest an interaction with the structural components of the interstitium, as well as an important role for the mast cells in the chain of events creating increased negativity of Pif.

Albumins↗

PubMed1993

Interstitial-lymphatic mechanisms in the control of extracellular fluid volume.

While the study of the physiochemical composition and structure of the interstitium on a molecular level is a large and important field in itself, the present review centered mainly on the functional consequences for the control of extracellular fluid volume. As pointed out in section I, a biological monitoring system for the total extracellular volume seems very unlikely because a major part of that volume is made up of multiple, separate, and functionally heterogeneous interstitial compartments. Even less likely is a selective volume control of each of these compartments by the nervous system. Instead, as shown by many studies cited in this review, a local autoregulation of interstitial volume is provided by automatic adjustment of the transcapillary Starling forces and lymph flow. Local vascular control of capillary pressure and surface area, of special importance in orthostasis, has been discussed in several recent reviews and was mentioned only briefly in this article. The gel-like consistency of the interstitium is attributed to glycosaminoglycans, in soft connective tissues mainly hyaluronan. However, the concept of a gel phase and a free fluid phase now seems to be replaced by the quantitatively more well-defined distribution spaces for glycosaminoglycans and plasma protein, apparently in osmotic equilibrium with each other. The protein-excluded space, determined mainly by the content of glycosaminoglycans and collagen, has been measured in vivo in many tissues, and the effect of exclusion on the oncotic buffering has been clarified. The effect of protein charge on its excluded volume and on interstitial hydraulic conductivity has been studied only in lungs and is only partly clarified. Of unknown functional importance is also the recent finding of a free interstitial hyaluronan pool with relatively rapid removal by lymph. The postulated preferential channels from capillaries to lymphatics have received little direct support. Thus the variation of plasma-to-lymph passage times for proteins may probably be ascribed to heterogeneity with respect to path length, linear velocity, and distribution volumes. Techniques for measuring interstitial fluid pressure have been refined and reevaluated, approaching some concensus on slightly negative control pressures in soft connective tissues (0 to -4 mmHg), zero, or slightly positive pressure in other tissues. Interstitial pressure-volume curves have been recorded in several tissues, and progress has been made in clarifying the dependency of interstitial compliance on glycosaminoglycan-osmotic pressure, collagen, and microfibrils.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Neurogenic inflammation in rat trachea is accompanied by increased negativity of interstitial fluid pressure.

The present experiments were performed to investigate whether neurogenic inflammation in rat trachea (with edema formation and protein extravasation when the circulation is intact) induced by electrical field stimulation of neuropeptide-containing C fibers in the vagal nerve is accompanied by increased negativity of interstitial fluid pressure (P(if)). Increased negativity of P(if) in the trachea occurs in dextran anaphylaxis and mast cell degranulation and facilitates edema formation under these circumstances. Experiments were performed after circulatory arrest had been induced in pentobarbital anesthesia to prevent edema formation, which will raise P(if) and potentially cause underestimation of an increased negativity of P(if). After induction of circulatory arrest, the vagal nerve was isolated and placed in a stimulating electrode. The trachea was then exposed and covered with mineral oil, and measurement of P(if) was started as soon as possible thereafter. P(if) was measured with sharpened glass capillaries (tip diameter, 3 to 7 microns) connected to a servocontrolled counterpressure system. P(if) in the control group (n = 12) did not change throughout the observation period. Electrical stimulation of the left vagal nerve caused P(if) to fall in all experiments, from -1.1 +/- 1.1 mm Hg in the control condition to an average of -10.6 +/- 3.4 mm Hg (n = 9, P < .01). In some experiments, a continuous recording of P(if) was obtained, showing that the reduction of P(if) started within 30 seconds after onset of stimulation to reach and later remain at a stable level within a few minutes. The experimental protocol was repeated after the C fibers had been nearly depleted of neuropeptides with capsaicin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Interstitial fluid pressure in rat skin becomes more negative in the initial phase of carrageenan-induced edema.

Increased negativity of the interstitial fluid pressure (P(i)) in the skin is a major driving force to create the initial edema in burn injury and, to a smaller degree, in the edemas formed in the initial phase of the chemical irritation induced by xylene and the anaphylactic reaction induced by dextran. The phenomenon of increased negativity of P(i) is the basis for stating that the connective tissues become 'active' in fluid exchange since the increased negativity of P(i) will be a major driving pressure for transcapillary fluid flux under these circumstances. The present study was performed to investigate if increased negativity of P(i) contributes to formation of the inflammatory edema induced by carrageenan in the rat paw skin, since carrageenan inflammation involves mechanisms principally different from burn injury, xylene and dextran anaphylaxis. Control P(i) averaged -0.42 mmHg +/- 0.12 (SE). Injection of normal saline increased P(i) by 1.4 mmHg in 6-10 min. In animals with intact circulation P(i) decreased to -4.75 +/- 0.60 mmHg in the same time period following subdermal injection of carrageenan and later returned to control values by 21-30 min. To prevent the edema formation which will increase P(i) and potentially lead to underestimation of an increased negativity in P(i), measurements were also performed after circulatory arrest when there will be no transcapillary fluid flux in response to the inflammatory agent. In this group P(i) fell to -4.10 +/- 0.71 mmHg (11-20 min) and remained at -2.75 to -4.10 mmHg throughout the observation period. Premedication with aprotinin (protease inhibitor), indomethacin (prostaglandin inhibitor) and 1,2 benzopyrone did not change the increased negativity in P(i) induced by carrageenan. In conclusion, the increased negativity of P(i) contributes to the formation of edema also in carrageenan-induced inflammation and is an effect of carrageenan which has previously not been described.

Animals↗

PubMed1992

Catabolism of hyaluronan in the knee joint of the rabbit.

Catabolism of hyaluronan was studied by injecting hyaluronan labelled with [125I]-tyramine cellobiose ([125I]-TC) into knee joints of rabbits. After endocytosis [125I]-TC remains intracellularly allowing localization of the site of catabolism. At 6 hours after injection 63% could be recovered in and around the joint, while at 48 hours 32% remained locally. Chromatography showed that 12% of the injected tracer was degraded in joint tissues at 6 hours, increasing to 33% at 24 hours. There was no apparent degradation within the joint fluid. No tracer was found in the regional lymph glands, but 16% of the injected tracer was detected in the liver at 24 hours. This investigation demonstrates that hyaluronan in the joint can be degraded both locally and in the liver.

Animals↗

PubMed1992

Estimation of total body fluid shifts between plasma and interstitium in man during extracorporeal circulation.

Fluid transport between plasma and interstitium during extracorporeal circulation was studied in seven patients undergoing aortocoronary bypass grafting. The absolute shifts in plasma volume during hypothermia were determined as the difference between input and loss of fluid and the changes in blood volume. The change in haemoglobin concentration due to acute haemodilution when starting extracorporeal circulation was used to calculate the absolute blood and plasma volume. The Starling equation for exchange across the capillary wall was used to describe fluid shifts. The total fluid filtered during the 60- to 90-min period of extracorporeal circulation averaged 34.1 +/- 11.1 (s.d.) ml/min. The total body filtration coefficient from the Starling relationship averaged 0.046 +/- 0.012 ml/kg.mmHg.min (0.354 +/- 0.092 ml/kg.kPa.min). Haemodilution, reducing colloid osmotic pressure in plasma (COPP) by approximately 10 mmHg (1.3 kPa) will result in a loss of plasma fluid of around 2 1 per hour. When corrected for lower fluid viscosity due to hypothermia during extracorporeal circulation, CFC would be about 40% higher, and a filtered volume of nearly 3 1 in a normothermic 70-kg person would be expected. Crystalloid haemodilution for shorter periods of time does not produce excessive oedema and thus may be well tolerated.

Aged↗

PubMed1992

Ileal microvascular permeability: a comparison of PS and sigma d using lymphatic and isotopic protein clearances.

Lymphatic clearances of total protein, albumin, immunoglobulin (Ig) G, and IgM obtained in autoperfused cat ileum as venous pressure (Pv) was elevated were analyzed using traditional methods as well as the newer maximal diffusion (max,diff) method of Reed et al. [Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H728-H740, 1991; Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1037-H1041, 1989] to determine capillary osmotic reflection coefficients (sigma d) and unique permeability surface area products (PS). In a control group (n = 6), sigma d max,diff and PSmax,diff for albumin, IgG, and IgM could not be determined due to their transiently high clearance patterns. These patterns were not altered by treatment with vasodilators (n = 6) to prevent redistribution of blood flow from the mucosal-submucosal to muscularis layer of the ileum, which accompanies elevation of ileal Pv. Furthermore, sigma d values for IgG in both groups were lower than those for both albumin and IgM, a finding inconsistent with predictions based on pore theory, together suggesting that lymphatic protein clearances were influenced by washout of interstitial proteins, a conclusion supported by the decrease in tissue content of albumin and IgG after elevation of Pv. Clearances of radiolabeled albumin (n = 10) and IgG (n = 6), measured after an initial 2-h steady-state period at a constant Pv, were markedly reduced at low lymph flow compared with those obtained in the shorter term experiments. In an additional group (n = 5), albumin clearance peaked at 10 times baseline within 15 min after a step increase in Pv to 30 mmHg but fell to only 3 times baseline within 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Increased lymphatic flux of hyaluronan from cat intestine during fat absorption.

During fat absorption, chylomicrons with sizes up to 5,000-10,000 A must traverse an interstitium that has estimated pore sizes of 120-200 A to reach the lacteals. The present experiments were performed to study the behavior of the interstitial matrix component hyaluronan during fat absorption from the intestine. Ileal segments were isolated and autoperfused in pentobarbital-anesthetized cats. A postnodal lymphatic was cannulated, and lymph flow, protein, and hyaluronan concentration in lymph were determined. In group 1, a mixture of oleic acid and taurocholate was infused into the ileal lumen, while in group 2 the animals were fed cream overnight. In group 1, control lymph flow and hyaluronan concentration averaged 53.3 +/- 16.0 (SD) microliters.min-1.100 g intestine-1 and 21.4 +/- 16.0 micrograms/ml, respectively. Administration of taurocholate and oleic acid increased lymph flow and lymph hyaluronan concentration by 100 and 50%, respectively, resulting in a nearly three-fold increase in hyaluronan flux. Subsequent increases in venous pressure increased lymph flow and reduced hyaluronan concentration in lymph to less than 3 micrograms/ml. Hyaluronan flux remained approximately 2 micrograms.min-1.100 g intestine-1 independent of lymph flow. In group 2, no lymph sample was available before administration of fat. Hyaluronan concentration at control venous pressure was 19.3 +/- 6.7 micrograms/ml and fell to 10 micrograms/ml at the highest lymph flow. Hyaluronan flux was approximately 10 micrograms.min-1.100 g intestine-1 at the highest lymph flow and venous pressure (P less than 0.05 compared with the same lymph flow in group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1992

Hyaluronan flux from cat intestine: changes with lymph flow.

Isolated and autoperfused ileal segments from pentobarbital-anesthetized cats were used to study turnover of hyaluronan in the intestine. A postnodal lymphatic was cannulated, and transcapillary and interstitial fluid fluxes were increased by raising venous pressure. Lymph hyaluronan concentration in control averaged 20.2 +/- 18.8 (SD) micrograms/ml (range 4.6-50) and increased with increasing lymph flow in all experiments to peak at concentrations two to three times above control values (at 15-20 mmHg increase in venous pressure). At higher lymph flows, hyaluronan concentration fell to below 5 micrograms/ml to an average of 21.3 +/- 19.5% of control value at the highest venous pressures used (30-40 mmHg). Tissue hyaluronan content fell from 349 +/- 191 micrograms/g dry wt in control to 148 +/- 78 micrograms/g dry wt (P less than 0.05) at the end of the experiment. In a second group, vasodilators were administered before elevation of venous pressure to prevent redistribution of blood flow between mucosal and muscular layers. The results were similar to those obtained above. In a third experimental group, venous pressure was elevated in one step to 30 mmHg and maintained at this level. Again, hyaluronan concentration initially increased and later fell well below control values. We conclude that a major part of the intestinal hyaluronan is easily mobilized by increased interstitial fluid flux.

Animals↗