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J R Levick

Publications and source records attributed to J R Levick.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effect of depletion of interstitial hyaluronan on hydraulic conductance in rabbit knee synovium.

1. The hydraulic resistance of the synovial lining to fluid outflow from a joint cavity (Qs) is important for the retention of intra-articular lubricant. The resistance has been attributed in part to extracellular glycosaminoglycans, including hyaluronan and chondroitin sulphates. Increased permeability in joints infused with testicular hyaluronidase, which digests both chondroitin sulphates and hyaluronan, supports this view. In this study the importance of interstitial hyaluronan per se was assessed using leech and Streptomyces hyaluronidases, which degrade only hyaluronan. 2. Ringer solution was infused into the knee joint cavity of anaesthetized rabbits for 30 min, with or without hyaluronidase, after which intra-articular pressure (Pj) was raised and the relation between pressure and outflow determined. 3. Treatment with Streptomyces, leech or testicular hyaluronidases increased the fluid escape rates by similar factors, namely 4- to 6-fold. After Streptomyces hyaluronidase treatment the slope d 8d s/dPj, which at low pressures represents synovial hydraulic conductance, increased from a control of 0.90 +/- 0.20 microl min-1 cmH2O-1 (mean +/- s.e.m. , n = 6) to 4.52 +/- 0.70 microl min-1 cmH2O-1. The slope d 8d s/dPj increased to a similar level after testicular hyaluronidase, namely to 4.14 +/- 1.06 microl min-1 cmH2O-1 (control, 0.54 +/- 0.24 microl min-1 cmH2O-1). Streptomyces and leech hyaluronidases were as effective as testicular hyaluronidase (no statistically significant differences) despite differences in substrate specificity. 4. It was shown using histochemical and immunohistochemical techniques that hyaluronan was removed from the synovium by leech, Streptomyces and testicular hyaluronidases. The binding of antibodies 2-B-6 and 3-B-3 showed that the core proteins of the chondroitin sulphate proteoglycans remained intact after treatment with hyaluronidases, and the binding of 5-D-4 showed that keratan sulphate was unaffected. An azocasein digestion assay confirmed that the hyaluronidase preparations had no significant proteolytic activity. 5. The effect of the hyaluronidases was four times greater than predicted from the low concentration of interstitial hyaluronan and its resistivity. Factors that might amplify the effect of hyaluronan depletion include the matrix-organizing role of hyaluronan, and/or non-uniformity of hyaluronan distribution. It is concluded that interstitial hyaluronan makes a major contribution to synovial hydraulic resistance, but the mechanisms are as yet poorly understood.

Animals↗
PubMed1998

Direct evidence for the partial reflection of hyaluronan molecules by the lining of rabbit knee joints during trans-synovial flow.

1. In synovial joints hydraulic and turnover studies indicate that the synovial lining may partially reflect large macromolecules like hyaluronan, despite discontinuities in the lining cell layer. The reflection hypothesis was tested directly in the present study. 2. Solutions of high molecular weight hyaluronan were infused at controlled pressures into the cavity of rabbit knees under anaesthesia, at concentrations of 0.2 g l-1 (n = 5), 2 g l-1 (n = 5) and 4 g l-1 (n = 6). Time-averaged trans-synovial flows were 9.6, 4. 8 and 2.9 microl min-1, respectively. After 5 h infusion the intra-articular fluid was mixed and sampled. Hyaluronan concentration was determined by size-exclusion chromatography. 3. In all sixteen experiments the hyaluronan concentration in the aspirate was greater than that in the infusate (P = 0.0001, Student's paired t test). The increases averaged 2.28 +/- 0.04 times at high filtration rates (0.2 g l-1 infusates; mean +/- S.E.M.), 1.60 +/- 0. 09 times at intermediate filtration rates (2 g l-1 infusates) and 1. 26 +/- 0.08 times at low filtration rates (4 g l-1 infusates). 4. Between 48 and 95 % of the hyaluronan in the filtrand was retained in the joint cavity. The greater retention at 2 g l-1, viz.95 %, than at 0.2 g l-1, viz.48 %, was attributed to interactions between overlapping molecular domains in the more concentrated solution. 5. It is concluded that synovial interstitial matrix can partially reflect hyaluronan molecules, and thus conserve intra-articular lubricant.

Animals↗
PubMed1998

The proteoglycans and glycosaminoglycan chains of rabbit synovium.

The synovial lining of joint capsules is important because it controls the flow of fluid into and out of the joint cavity. Physiological studies have shown that the glycosaminoglycans, particularly hyaluronan, have an important role in the control of fluid flow. The distribution of the glycosaminoglycans and proteoglycans in the synovium and subsynovium of rabbits (approximately 12 weeks old) was, therefore, determined immunohistochemically. Hyaluronan, chondroitin-4- and chondroitin-6-sulphates and keratan sulphate are present in the synovium and subsynovium; chondroitin-4-sulphate is at higher concentrations than chondroitin-6-sulphate. The core proteins of the chondroitin sulphate proteoglycans, biglycan and decorin, and of the keratan sulphate proteoglycan, fibromodulin, are also present. To date, fibromodulin has not been located in other synovial linings, and its presence corroborates that of keratan sulphate.

Animals↗
PubMed1998

A method for estimating macromolecular reflection by human synovium, using measurements of intra-articular half lives.

Recent studies show that very large macromolecules in synovial fluid, such as hyaluronan and large proteoglycans, are partially reflected by the synovial lining during fluid drainage, and thus selectively retained within the cavity. Size selective molecular reflection is a fundamental property of membranes, and a method for quantifying the reflective behaviour of human synovium could be of value in several pathophysiological areas. The method proposed here is based on the intra-articular half lives of the macromolecule of interest and of a smaller, easily cleared protein such as albumin. The key relation is derived from the law of conservation of mass, using simple algebra. It is found that, when the intra-articular half lives of albumin and a macromolecular test solute are determined simultaneously, the reflected fraction of the test solute is given by the complement of the half life ratio. Examples are given. Intra-articular half lives can thus be used to consider such questions as whether immune complexes are significantly reflected by the synovial surface, how the reflective property changes in arthritides or with treatment, and how significantly reflection might influence the intra-articular concentration of large "markers" of joint disease activity.

Half-Life↗
PubMed1998

Forearm blood flow measured by venous occlusion plethysmography in healthy subjects and in women with postmastectomy oedema.

A chronic swelling of the arm may develop following damage to axillary lymph vessels during breast cancer treatment. Certain unusual pathophysiological features of postmastectomy oedema indicate that factors additional to lymphatic damage are important. One factor postulated previously is a haemodynamic abnormality. Forearm blood flow was therefore measured by venous occlusion plethysmography using both a conventional mercury strain gauge and a newer optical volumeter (Perometer). The latter was initially assessed in healthy subjects. When forearm blood flow was measured using the two methods simultaneously, the strain gauge and Perometer did not differ significantly for healthy or oedematous arms. Dominant and non-dominant arm blood flow in healthy subjects was similar but with greater variation between sides with the Perometer. Using the strain gauge, blood flow in the oedematous arm (2.51 +/- 1.33 ml/100 ml per min) was significantly lower than in the opposite unaffected arm (3.77 +/- 2.29 ml/100 ml per min; p = 0.026). The Perometer results showed a similar but nonsignificant trend (p = 0.105). Taking into account the greater limb volume on the affected side, total forearm blood flow was essentially the same in each arm (unaffected: 40.72 +/- 28.70 micromilligrams/min; oedematous: 41.78 +/- 22.11 ml/min). The reduced blood flow per unit volume of arm was therefore likely to be due to a simple 'dilution' effect of the increase in volume. The results indicate that it is unlikely that raised blood flow contributes to oedema formation, contrary to the haemodynamic concept.

Adult↗
PubMed1997

Hyaluronan secretion into the synovial cavity of rabbit knees and comparison with albumin turnover.

1. Hyaluronan is not only a lubricant but also enhances the synovial lining's resistance to fluid outflow. This finding led to the proposal that hyaluronan (> 2 x 10(6) Da, approximately 210 nm radius) may escape across the synovial lining less freely than smaller solutes (e.g. albumin, 6.7 x 10(4) Da, 3.6 nm radius) or water. Here multiple washouts were used to measure intraarticular hyaluronan mass and secretion rate in rabbit knees, leading to an estimate of hyaluronan turnover time. Plasma albumin permeation into the joint cavity was also measured to enable comparison of turnover times between molecules of very disparate size. 2. Endogenous hyaluronan mass in the joint cavity, analysed by high performance liquid chromatography of joint washes, was 182 +/- 9.9 micrograms (mean +/- S.E.M; n = 21). Since hyaluronan concentration in synovial fluid averages 3.62 +/- 0.19 micrograms microliters-1, the endogenous synovial fluid volume was calculated to be 50 microliters (mass/concentration), about double the aspiratable volume. 3. The hyaluronan secretion rate over 4 h was 4.80 +/- 0.77 micrograms h-1 (n = 5). The rate was significantly higher in contralateral joints expanded by 2 ml Ringer solution (5.80 +/- 0.84 micrograms h-1, n = 5, P = 0.01, Student's paired t test), indicating a stretch/hydration sensitive secretory mechanism. The newly secreted chains ((2.05-2.48) x 10(6) Da) were not significantly different in length from the endogenous chains (2.95 x 10(6) Da). 4. Hyaluronan turnover time, calculated as mass/secretion rate, was 31.4-37.9 h. This is more than an order of magnitude longer than turnover time for intra-articular albumin. The latter, determined from the intra-articular albumin mass and plasma-to-cavity permeation rate was 1.8 h (95% confidence intervals 1.2-3.5 h, n = 9). The big difference in turnover times support the view that, relative to albumin and water, hyaluronan is partially sieved out and retained in the joint cavity by the synovial lining. The lining cell layer is discontinuous, so it appears that interstitial matrix itself acts as a leaky size-selective molecular filter.

Animals↗
PubMed1997

Quantification of the initial lymphatic network in normal human forearm skin using fluorescence microlymphography and stereological methods.

Fluorescence microlymphography enables the visualization of the initial lymphatic network in human dermis in vivo. In order to determine which objective, measurable parameters are likely to be of value in future studies, microlymphangiograms were obtained from normal forearm skin of eight men and nine women of a range of ages and analyzed stereologically to calculate: (1) lymphatic length density at a specified radial distance, r, from the site of injection of the fluorescent dye (LDr, cm-1); (2) maximum lymphatic density (LDmax, cm-1); (3) total length of filled lymphatic (LL, cm); (4) maximum radial spread of vessels (mm). There was no significant difference between the right and left arms for peak LDr, LDmax, LL, or spread. Mean values (+/-SD) for the right and left arms combined (n = 24) were 13.34 +/- 7.61 cm-1; 19.31 +/- 8.96 cm-1; 12.04 +/- 10.04 cm; and 7.58 +/- 3.30 mm, respectively. Unexpectedly, three of the four parameters were significantly lower in women compared to men. For women LDmax was 30% lower than for men (P = 0.04), LL was 59% lower (P = 0.032), and spread was 39% lower (P = 0.007). Peak LDr did not differ significantly. Stereological analysis of fluorescent microlymphangiograms enables quantification of the dermal initial lymphatic network and hence the objective study of the influence of gender, age, and disease (including treatment interventions).

Adult↗
PubMed1997

Glycosaminoglycan depletion greatly raises the hydraulic permeability of rabbit joint synovial lining.

The hydraulic resistance of the synovial lining of a joint is important for retention of intraarticular lubricant. The resistance has been attributed to synovial interstitial glycosaminoglycans. This was tested by depletion of hyaluronan and chondroitin sulphates from synovium in five rabbit knees in vivo under anaesthesia, using testicular hyaluronidase. The enzyme raised synovial permeability to fluid 5- to 7-fold-substantially more, in fact, than predicted by a recent model. The results prove that hyaluronan and/or chondroitin sulphate are important sources of hydraulic resistance in synovium.

Animals↗
PubMed1997

Fluid exchange across endothelium.

The fluid pathway between plasma and lymph comprises 3 matrices of biopolymer chains arranged in series (endothelial glycocalyx, basement membrane, interstitial matrix), each of differing area, thickness, density and biochemical composition. Fluid exchange obeys the Starling principle but the 'balance' of pressures commonly favours filtration even 'downstream', and not venular reabsorption as still widely mistaught. At tissue level the maintenance of fluid balance remains controversial. The 3-pore theory is reviewed and updated following aquaporin characterisation. The permeability of the endothelial layer can be altered by both intracellular (Ca2+i and cyclic nucleotides) and extracellular mechanisms (albumin, orosomucoid), leading to gross 'hole' formation through as well as between cells (inflammatory stimuli) or more subtle changes (e.g. atrial natriuretic peptide). This is currently a fertile zone of interaction between classical physiology and molecular studies.

Biological Transport↗
PubMed1997

Chronic arm edema following breast cancer treatment.

Chronic edema of the arm (postmastectomy edema, PME) is a common and incurable complication of breast cancer treatment, often developing without warning months or years later. Although the original cause of PME is damage to axillary lymph drainage routes by surgery and radiotherapy, many observations suggest that additional factors are involved. Recent attention has focused on the Starling forces in the skin and subcutis in PME. An important finding was that the protein concentration, and hence colloid osmotic pressure, of the subcutaneous interstitial fluid of the PMF arm is unexpectedly lower than in the unaffected arm, correlating negatively with the degree of swelling. There are several possible explanations for this, such as a rise in capillary filtration rate, or interstitial proteolysis. A systemic component to PME is suggested by the finding of a lower plasma protein concentration in affected women compared with a matched postmastectomy group without swelling. A recent study using intra-vital capillaroscopy has indicated that angiogenesis occurs in the skin in PME, and an increased capillary surface area for filtration could result in an increased fluid load on a compromised lymph drainage system. Further elucidation of the pathophysiological processes in PME, in particular the adjustments to Starling forces, will enable more effective therapy of this distressing condition.

Arm↗
PubMed1997

Validation of an optoelectronic limb volumeter (Perometer).

The Perometer, a device designed for the measurement of limb volume, has been rigorously assessed by comparison with other methods. Differences in the volume of geometric shapes and limbs determined by the Perometer and a tape measure/meter rule (i.e., Perometer minus direct measurement) were -0.8 to 2.4% (cylinders), -4.6% (truncated cone), -3.3% (mannequin limbs), 6.1% (normal human arms) and 6.8% (lymphedema arms). The larger differences were likely to be due to deviation from circular or elliptical cross-section (Perometer or tape method) and compression of the arm (tape method). Errors arising from incorrect positioning within the measuring frame were generally small, but large errors occurred when a cylinder was partially rotated within the frame (i.e., no longer perpendicular to the light beams). The Perometer was highly reproducible, each measurement taking only a few seconds. When recording the change in volume with time of a segment of arm during venous occlusion (blood flow measurement by venous occlusion plethysmography) using the Perometer plus a mercury strain gauge, between-method differences for individual blood flow recordings were apparent. The source of these differences is discussed. However, using the average of a number of blood flow recordings the Perometer and the strain gauge agreed fairly closely for both the normal and lymphedema arms. The Perometer is thus a reliable and convenient tool for the measurement of limb volume, and may also be used to measure the rate of swelling during venous occlusion plethysmography.

Adult↗
PubMed1996

Glycosaminoglycan concentration in synovium and other tissues of rabbit knee in relation to synovial hydraulic resistance.

1. The hydraulic resistance of the synovial lining of a joint, a key coupling coefficient in synovial fluid turnover, is thought to depend on the concentration of biopolymers (glycosaminoglycans (GAGs) and collagen) in the synovial intercellular spaces, because these polymers create hydraulic drag. The primary aim of this study was to obtain microscopically separated, milligram samples of the very thin synovium from eight rabbit knees, and to analyse these quantitatively for GAGs (chondroitin sulphate, heparan sulphate and hyaluronan) and collagen to allow comparison with published hydraulic resistance data. Synovial fluid and femoral cartilage were also studied. 2. Synovium comprised 73 +/- 3% water by weight (mean +/- S.E.M.). Of the 270 mg solid per gram of wet tissue, protein formed 136 mg (by automated amino acid analysis), and of this 94 mg was collagen by hydroxyproline analysis. From the collagen mass and fibril volume fraction (0.153 of tissue by morphometry), fibrillar specific volume was calculated to be 1.43 ml per gram of molecular collagen, and fibril water content 47% by volume. 3. The concentration of chondroitin 4-sulphate (C4S) plus chondroitin 6-sulphate (C6S), measured by capillary zone electrophoresis was 0.55 mg per gram of synovium--much greater than in synovial fluid (0.04 mg g-1) and much less than in cartilage (27.8 mg g-1). The C4S/C6S ratio in synovium (7.3) differed from that in cartilage (0.7), indicating that different proteoglycans predominated in synovium. The heparan sulphate concentration, assayed by radioactive Ruthenium Red binding, was 0.92 mg per gram of synovium (synovial fluid, 0.08 mg g-1; cartilage, 0.72 mg g-1). 4. In contrast to sulphated GAGs, the hyaluronan concentration was highest in synovial fluid (3.53 mg g-1; biotinylated G1 domain binding assay). The concentration in synovial interstitium was only 0.56 mg g-1 (corrected for interstitial volume fraction, 0.66), even though there is open contact between synovial interstitium and synovial fluid. This may be due to exclusion or washout. 5. Total GAG mass was approximately 4 mg per gram of synovial interstitium. A model of trans-synovial flow indicated that a uniform GAG concentration of 4 mg g-1 is less than 1/3rd of that required to explain the experimental estimate of synovial hydraulic resistance. Errors in the resistance estimate do not appear to be large enough to resolve the problem. It is possible, therefore, that additional polymeric material in the interstitium, such as glycoproteins and proteoglycan core protein, may contribute to the hydraulic resistance.

Animals↗
PubMed1996

Changes in glycosaminoglycan concentration and synovial permeability at raised intra-articular pressure in rabbit knees.

1. When intra-articular pressure is raised to pathological values (> 9 cmH2O) by saline, the hydraulic conductance of the synovial lining increases manyfold. The increase at 25 cmH2O is only partially accounted for by stretching of the tissue and has been ascribed to washout and/or dilution of interstitial matrix biopolymers. This suggestion was tested in this study by sampling synovium from control joints (rabbit knees) and from joints perfused with saline to 25 cmH2O, and analysing them quantitatively for collagen, chondroitin sulphate, heparan sulphate and hyaluronan. 2. Pressure and trans-synovial flow measurements showed that in samples taken at 25 cmH2O the conductance of the synovial lining had increased by a factor of 5.23 +/- 1.5 (mean +/- S.E.M.) over the conductance at low pressures (just above atmospheric pressure). 3. The tissue concentrations of collagen and the sulphated glycosaminoglycans (GAGs) were reduced by similar amounts after perfusion to 25 cmH2O, namely to 62.8-70.4% of control. The hyaluronan concentration by contrast was not significantly reduced (106% of control). 4. The reduction in collagen concentration (fixed material) indicated increased interstitial hydration. The closely similar reduction in sulphated GAGs indicated that dilution rather than washout of these components was occurring. The hyaluronan results could be explained by synthesis in vivo at a rate of > or = 91 micrograms h-1 (ml synovium)-1 (possibly a non-basal rate under the conditions of the experiment, i.e. raised pressure and a stretched hydrated membrane). 5. Because interstitial hydraulic drag is related to biopolymer concentration by a power function, the overall matrix dilution observed here was more than sufficient to explain the rise in synovial lining hydraulic conductance at 25 cmH2O when taken in conjunction with stretching of the synovial lining (increased area, reduced thickness).

Animals↗
PubMed1996

Cutaneous vascular control in the arms of women with postmastectomy oedema.

The control of forearm skin blood flow was examined in the swollen arms of twelve women with oedema caused by breast cancer treatment. The swollen arm was compared with the opposite unaffected (control) arm. Using laser Doppler flux (LDF) and continuous finger blood pressure (BP) measurements, vascular control was tested by applying a range of provocations previously shown to alter cutaneous vascular resistance (CVR) in healthy subjects. The tests and the accepted mechanism were: post-ischaemic hyperaemia (locally mediated vasodilatation), inspiratory gasp and cool reflex (both sympathetically mediated vasoconstriction), arm dependency (locally mediated vasoconstriction), and core heat load (sympathetically mediated vasodilatation). CVR was calculated as BP/(LDF-biological zero). Three differences between the control and swollen arms were identified. (i) The laser Doppler biological zero signal was significantly higher on the swollen side (P = 0.005, Student's paired t test). (ii) Baseline LDF was significantly lower on the swollen side (P = 0.002), and apparent CVR correspondingly higher. (iii) Cumulative reactive hyperaemia (area under the LDF curve above baseline) was significantly less on the swollen side (P = 0.03), although peak flux was not significantly different. Inspiratory gasp, cool reflex, arm dependency and core heat load produced changes of similar magnitude in both arms. It appears that sympathetic neural control and local vasoconstrictor control in arm dependency are normal in arm lymphoedema but that locally mediated vasodilator control is impaired. In addition, baseline skin blood flow may be reduced in this condition. The results provide no support for impairment of vascular tone as a contributory factor to the oedematous state.

Aged↗
PubMed1995

Effect of intra-articular hyaluronan on pressure-flow relation across synovium in anaesthetized rabbits.

1. Hyaluronan is the major polysaccharide of synovial fluid, responsible for its high viscosity. The effect of hyaluronan on fluid transport across the synovial lining of the joint was investigated. Rate of fluid absorption from the joint cavity (Qs) was measured at intra-articular pressures (Pj) of up to 24 cmH2O in knees of anaesthetized rabbits, in the presence or absence of hyaluronan in intra-articular infusates. 2. Viscometry studies in vitro showed that the commercial hyaluronan used had a molecular weight of 549,000-774,000, a radius of gyration of 48-99 nm and a critical concentration for molecular overlap of 1.3 g l-1. 3. With intra-articular Krebs solution (control) or subnormal, subcritical concentrations of hyaluronan (0.5 g l-1), flow increased with pressure. Hyaluronan reduced the fluid escape rate by reducing slope dQs/dPj by 32-64% relative to Krebs solution. 4. At normal to high hyaluronan concentrations (3-6 g l-1) and low pressures, hyaluronan again reduced slope dQs/dPj, by 39-64%. The reduction in slope was slight, however, when compared with the reduction in bulk fluidity (1/relative viscosity). Fluidity at high shear rates was reduced to 6% of control values by 6 g l-1 hyaluronan. The effect on slope did not correlate significantly with the effect on fluidity. 5. At pressures above approximately 12 cmH2O, 3-6 g l-1 hyaluronan altered the shape of the pressure-flow relation: a flow plateau developed. In some joints raising pressure even reduced trans-synovial flow slightly. The pressure required to drive unit trans-synovial flow (an index of outflow resistance) increased 2.5-fold between 5 and 25 cmH2O in the presence of hyaluronan. By contrast, in the absence of hyaluronan the outflow resistance fell as pressure was raised. 6. It is suggested that the increasing resistance to flow in the presence of hyaluronan may be caused by partial molecular sieving of hyaluronan by the small porosities of the synovial interstitial matrix, leading to accumulation of a resistive filter cake of hyaluronan chains at the tissue-cavity interface. Since hyaluronan impedes fluid escape when pressure is raised, it may serve to preserve synovial fluid volume in vivo, e.g. during sustained joint flexion.

Anesthesia↗
PubMed1995

Assessment of noninvasive tests of cutaneous vascular control in the forearm using a laser Doppler meter and a Finapres blood pressure monitor.

The control of human forearm cutaneous vascular resistance was examined using a combination of laser Doppler perfusion measurement and continuous Finapres blood pressure measurement. Tests which provoke changes in blood flow via different control mechanisms (local and neural) were applied in a group of ten healthy subjects. The purpose was to select from them a suitable (i.e. statistically significant) group to apply in cases where a disease process is suspected of interfering with the control of the skin circulation. Deep inspiration, immersion of the feet in water at 15 degrees C (both eliciting sympathetic vasoconstrictor nerve activity) and arm dependency (eliciting the local veni-arteriolar response) produced statistically significant, symmetrical increases in cutaneous vascular resistance in both arms (p < 0.05, Wilcoxon's test for paired differences). Similarly, post-ischaemic reactive hyperaemia (mediated by local vasodilator mechanisms) and indirect heating of the body (eliciting increased sympathetic vasodilator nerve activity) resulted in significant decreases in cutaneous vascular resistance (p < 0.01). When deep inspiration was repeated from a vasodilated baseline after indirect heating, the increases in cutaneous vascular resistance were smaller than those obtained before heating. Isometric handgrip exercise failed to produce a significant change in contralateral cutaneous vascular resistance (p > 0.05). There were no differences between right and left arms for any test (p > 0.05). The successful tests were subjected to power analysis in order to predict likely patient sample sizes required to demonstrate altered responsiveness at sites of microcirculatory disturbance compared with normal skin.

Adult↗
PubMed1995

Radial organization of interstitial exchange pathway and influence of collagen in synovium.

The synovial intercellular space is the path by which water, nutrients, cytokines, and macromolecules enter and leave the joint cavity. In this study two structural factors influencing synovial permeability were quantified by morphometry (Delesse's principle) of synovial electronmicrographs (rabbit knee), namely interstitial volume fraction Vv.1 and the fraction of the interstitium obstructed by collagen fibrils. Mean Vv.1 across the full thickness was 0.66 +/- 0.03 SEM (n = 11); but Vv.1 actually varied systematically with depth normal to the surface, increasing nonlinearly from 0.40 +/- 0.04 (n = 5 joints) near the free surface to 0.92 +/- 0.02 near the subsynovial interface. Tending to offset this increase in transport space, however, the space "blocked" by collagen fibrils also increased nonlinearly with depth. Bundles of collagen fibrils occupied 13.6 +/- 2.4% of interstitial volume close to the free surface but 49 +/- 4.8% near the subsynovial surface (full-thickness average, 40.5 +/- 3.5%), with fibrils accounting for 48.6-57.1% of the bundle space. Because of the two counteracting compositional gradients, the space available for fibril-excluded transport (hydraulic flow and macromolecular diffusion) was relatively constant > 4 microns below the surface but constricted at the synovium-cavity interface. The space available to extracellular polymers was only 51-53% of tissue volume, raising their effective concentration and hence the lining's resistance to flow and ability to confine the synovial fluid.

Animals↗