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

Abstract

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 cmH20, 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 + 1P5 (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 628 -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 > 91 jug 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).The hydraulic conductance of the synovial lining couples trans-synovial fluid movement to intra-articular pressure and is thus an important factor in synovial fluid dynamics. Measurements of trans-synovial flow in the rabbit knee, both in vivo and post mortem, show that the conductance of the synovial lining increases when intra-articular pressure is raised to pathological levels (above -9 cmH2O), such as occurs in joint effusions (Edlund, 1949). This causes a marked steepening of the pressure-flow relation and faster trans-synovial flows ('yield' phenomenon). Above -9 cmH2O each successive, applied step in pressure causes an increment in conductance to a new level, i.e. the pressure-conductance relation is graded above -9 cmH2O (Levick, 1980). A monotonic relation between conductance and intra-articular pressure above -9 cmH2O has been confirmed by measurements of blood-to-joint cavity conductance, i.e.

Pro- and anti-inflammatory cytokines increase hyaluronan production by rat synovial membrane in vitro

“…Taking into account the large volume of incubation medium (1 ml) in comparison to the volume of synovial fluid in the joint cavity, the equilibrium between the synovial membrane and its surroundings could not be restored to the in vivo level, and the HA content in the synovial membrane could not return to its initial value even when HASs were strongly activated. In general, our results agree with theories (54,55) that synovial lining cells contain a sensor which detects changes in HA concentration in synovial fluid and activates HASs when it drops below a physiological level.…”

“…The rate of secretion is significantly higher in joints expanded by injection of saline which suggests existence of a compensatory mechanism which aids to combat a fall in HA concentration (54,55). This mechanism may involve static stretch since HA secretion is mechanosensitive (56).…”

Contribution of F‐Actin to Barrier Properties of the Blood‐Joint Pathway

“…The pressureflow relation for control solutions containing DMSO at 0.5-5.0% (0.77 ± 0.15 L min −1 cmH 2 O −1 ) was within the range for DMSO-free controls in a previous work (41). There was no significant relation between DMSO in the control solutions during the range 0-5% and control dQ s /dP j (regression −0.04 ± 0.08 L min , p ‫ס‬ 0.95, n ‫ס‬ 8).…”

Influence of Actin Cytoskeleton on Intra-articular and Interstitial Fluid Pressures in Synovial Joints

“…The extent to which intra-articular pressure can be expected to mirror changes in periarticular swelling pressure depends on the relative volume and compliance of the synovial cavity and the periarticular tissue. Calculations using estimates of compartment volumes and compliance from Knight and Levick, (1982), Levick and McDonald (1989a, b), Price et al (1996), and Scott et al (2000b) indicate that if the synovium and subsynovium developed an extra Ϫ2.7 cm H 2 O swelling pressure, the intra-articular pressure would change by Ϫ1.6 cm H 2 O, given an injection volume of 10 l at subatmospheric joint pressure (the optimal conditions for detecting the putative effect). Despite its inferred detectability, no such response was seen.…”