Relation Between Trans‐synovial Flow and Plasma Osmotic Pressure, With an Estimation of the Albumin Reflection Coefficient in the Rabbit Knee

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.

mentioning

confidence: 74%

Section: Intra-articular Pressure and Trans-synovial Flow Measurementmentioning

confidence: 99%

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

Price

Levick

Mason

1996

“…Fenestrated vesicles, transcellular gaps (Neal & Michel, 1997), or unfenestrated, vesiculo-vacuolar organelles (Feng et al 1997) have also been reported. The quantitative sieving properties of these ultrastructural changes during VEGF perfusion are unknown, but the reflection coefficient to albumin of fenestrated capillaries is 0·78 in both the knee joint (Knight et al 1988) and the ascending vasa recta (Pallone, 1992), and the sieving properties of fenestrated endothelium of the glomerulus remain intact with a high reflection coefficient to albumin (Savin et al 1992). These previously published findings are therefore consistent with the results described here.…”

Section: Discussionmentioning

confidence: 99%

The chronic effect of vascular endothelial growth factor on individually perfused frog mesenteric microvessels

Bates

1998

Hydraulic conductivity (Lp) of the wall of perfused microvessels has previously been shown to be chronically increased 24 h after a 10 min perfusion with vascular endothelial growth factor (VEGF). In order to investigate this further, Lp and the effective oncotic pressure difference (σΔΠ) acting across the vessel walls was measured before exposure to VEGF and 24 h later after the mesentery had been replaced in the abdominal cavity. Acute 10 min perfusion with VEGF did not chronically change σΔΠ despite chronically increasing Lp 6.8 ± 1.2‐fold. This suggests that pathways formed 24 h after perfusion with VEGF which increase hydraulic conductivity of the capillary walls have the same reflection coefficient as those present before VEGF. Acute 10 min perfusion with VEGF significantly increased the diameter of vessels after 24 h by 48 ± 13 %. To determine whether this was due to changes in the compliance of the vessel wall, the distensibility of microvessels was measured before and 24 h after perfusion with VEGF. The distensibility was increased 45 ± 15 % by VEGF but this was not great enough to account for the increase in diameter. The chronic increase in Lp could be attenuated by inhibition of nitric oxide synthase with l‐NAME. In addition, the chronic increase in permeability was correlated with the acute response to VEGF (r= 0.71, P < 0.01) suggesting that the acute and chronic changes may be related. These results show that VEGF chronically increases Lp without affecting the oncotic reflection coefficient. This may be due to reduced pore path length, or increased small pore numbers, which are properties of fenestrated capillaries. They also show that VEGF increases microvascular distensibility and diameter.

“…where d V/dPj is the mean compliance of the rabbit synovial cavity at that pressure (Knight & Levick, 1982 Knight, Levick & McDonald, 1988). Five concentrations were investigated (10, 22-5, 55, 110, 150 g l-) and five to six animals were studied at each concentration.…”

Section: Methods In Vitromentioning

confidence: 99%

Effect of extravascular plasma protein on pressure‐flow relations across synovium in anaesthetized rabbits.

McDonald

Levick

1993

SUMMARY1. The effect of extravascular plasma protein on fluid flux through interstitial matrix was investigated in vivo by studying the pressure-flow relation across synovium during intra-articular infusions of protein solutions (usually bovine serum albumin). Synovium is a sheet of non-epithelial cells separated by interstitium-filled gaps, beneath which are fenestrated capillaries: synovium regulates synovial fluid volume and composition.2. Albumin solutions (10-150 g l-) of measured oncotic pressure and viscosity were infused at known pressure into the synovial cavity of knees of anaesthetized rabbits. Flow across the synovial lining in the steady state (absorption rate Q8) was recorded at a series of joint pressures (Ps) to define the pressure-flow relation. Krebs solution was infused into the opposite knee as a control (26 animals).3. Infusion of a low albumin concentration (10 g l-, bovine or rabbit) or diluted rabbit serum revealed no specific effect of plasma protein on interstitial matrix permeability (cf. specific protein effect on capillary glycocalyx permeability). Physiological (22-5 g l-') and higher concentrations reduced trans-synovial absorption rate. The slope of the pressure-flow relation was reduced and the pressure intercept displaced to the right (i.e. P, at zero flow was raised).4. Slope dQo/dP, correlated negatively with intra-articular viscosity (P= 0-001-0-04), in keeping with viscous interstitial flow. The reduction in normalized slope, however, did not equal the reduction in fluidity (1/viscosity) quantitatively. It is proposed that apparent fluidity within the interstitial matrix is higher than in the bulk phase due to steric exclusion of albumin (radius 3-55 nm) by the interstitial glycosaminoglycans. The latter form spaces of estimated mean hydraulic radius 14-18 nm in synovium.5. The joint-pressure intercept at zero net trans-synovial flow was displaced 0.015 cmH20 per cmH20 intra-articular oncotic pressure (nr,; S.E.M. + 0-006). Thus large trans-synovial osmotic gradients were not maintained at physiological flow velocities. The 1-5 % displacement of the P, intercept by nr, was attributed principally to interstitial albumin exerting pericapillary oncotic pressure and enhancing net Starling filtration pressure. Indeed, net trans-synovial flow at low