title: Effect of intra-articular hyaluronan on pressure-flow relation across synovium in anaesthetized rabbits.
abstract: 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.
authors.affiliation: Department of Physiology, St George's Hospital Medical School, London, UK.
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; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007270:Injections, Intra-Articular; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology; D008970:Molecular Weight; D009997:Osmotic Pressure; D011312:Pressure; D011817:Rabbits; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*; D014783:Viscosity
chemical_list: D006820:Hyaluronic Acid