Effect of fluid pressure on the hydraulic conductance of interstitium and fenestrated endothelium in the rabbit knee.

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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.

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confidence: 73%

Section: Resultsmentioning

confidence: 99%

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

Price

Levick

Mason

1996

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“…PO and hence AP, could vary directly with Jv/A, however, and this could be a consequence of Knight & Levick's (1985) conclusion that in many tissues the hydraulic resistance of the interstitial space is comparable with that of the capillary wall. If Ri represents the hydraulic resistance between a point in the pericapillary space where P = PO and a distant point in the system which is always at atmospheric pressure, then PO = Ri (Jv/A).…”

Section: Discussionmentioning

confidence: 96%

Steady‐state fluid filtration at different capillary pressures in perfused frog mesenteric capillaries.

Michel

Phillips

1987

128

101

SUMMARY1. The theory of steady-state filtration through capillary walls (Michel, 1984) P, less than the perfusate oncotic pressure, the transient data showed reabsorption of fluid from the tissues, but in the steady state either fluid movements were so small as to be undetected or slight filtration was observed. The steady-state data followed the pattern predicted by theory.4. The transient data were used to estimate the reflection coefficient ofthe capillary wall (o-) to the macromolecular solute. In seven vessels, the mean o-to BSA was 0-76 (S.E. of mean + 0-04) and in eight different vessels mean a to Ficoll 70 in the presence of BSA (10 mg ml-') was 0-98 (s.E. of mean +0 05). The steady-state data were consistent with the prediction that the oncotic pressure opposing high filtration rates approximates to o-21Ic in the steady state, where Hc is the perfusate oncotic pressure.

“…(i) Extravascular albumin reduces interstitial fluidity, causing viscous damping of fluid exchange. Substitution of conductivity x fluidity for interstitial conductance in the heuristic model of Knight & Levick (1985; eqn (1A)) confirms that (dQs/dirT)p=o contains an interstitial fluidity term and decreases as fluidity decreases: but numerical substitution indicates that fluidities of 0X8-0X5 reduce (dQ1/d1)p~o by at most 5-18 % relative to dQ/dnp, when pericapillary albumin dilution is not considered. (ii) A rise in mean capillary Up as plasma filtration fraction rises (haemoconcentration) may also buffer (dQ1/d7rT)P=0.…”

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confidence: 92%

“…The reason relates to the fact that slope dQ8/dPj above yield pressure is a compound parameter; it does not represent a simple hydraulic conductance, because conductance increases as a continuous function of joint pressure above yield point (Knight & Levick, 1985). Even with a minimalistic one-dimensional model (a variable intimal interstitial resistance in series with two parallel resistances, one across the capillary wall and one through deeper interstitium into subsynovium), the expression for dQ/dPj above yield pressure is a composite term involving oncotic pressure gradients as well as conductances, as expressed by eqn (4A) of Knight & Levick (1985). Re-expressing interstitial conductance as conductivity x fluidity, the one-dimensional model predicts that the relation between fractional slope and fluidity is steeper above yield pressure than below it, in keeping with the experimental observations in Fig.…”

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confidence: 99%

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

McDonald

Levick

1993

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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