title: Effect of extravascular plasma protein on pressure-flow relations across synovium in anaesthetized rabbits.
abstract: 1. 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-1) 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 Qs) was recorded at a series of joint pressures (Pj) 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-1, 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-1) 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. Pj at zero flow was raised). 4. Slope dQs/dPj 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 cmH2O per cmH2O intra-articular oncotic pressure (pi j; S.E.M. +/- 0.006). Thus large trans-synovial osmotic gradients were not maintained at physiological flow velocities. The 1.5% displacement of the Pj intercept by pi j was attributed principally to interstitial albumin exerting pericapillary oncotic pressure and enhancing net Starling filtration pressure. Indeed, net trans-synovial flow at low joint pressure sometimes reversed from absorption to filtration into the joint cavity at high intra-articular oncotic pressures. 6. The displacement of the trans-synovial flow intercept per unit change in intra-articular oncotic pressure, (dQs/d pi j)Pj = 0, was 18 +/- 3 nl min-1 cmH2O-1.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Physiology, St George's Hospital Medical School, London.
authors.forename: J N
authors.initials: JN
authors.lastname: McDonald
authors.forename: J R
authors.initials: JR
authors.lastname: Levick
mesh_terms: D000758:Anesthesia; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D008297:Male; D009997:Osmotic Pressure; D010539:Permeability; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*; D014783:Viscosity
chemical_list: D001798:Blood Proteins; D012710:Serum Albumin, Bovine