Characterization of the effect of high molecular weight hyaluronan on trans-synovial flow in rabbit knees

1. The effect of a rooster comb hyaluronan (3.6-4.0 g l(-1)) of similar chain length to rabbit synovial fluid hyaluronan, on the trans-synovial escape of fluid from the joint cavity in the steady state ((Q) over dot(s)) was studied in 29 rabbit knees at controlled intra-articular pressures (P-j). 2. Rooster hyaluronan caused the pressure-flow relation to flatten out as pressure was raised. At 10-20 cmH(2)O the slope of the quasi-plateau, 0.05 +/- 0.01 mu l min(-1) cmH(2)O(-1) (mean +/- S.E.M), was 1/39th that for Ringer solution (1.94 +/- 0.01 mu l min(-1) cmH(2)O(-1)). 3. Bovine synovial fluid had a similar effect to hyaluronan in Ringer solution. 4. The quasi-plateau was caused by increasing opposition to outflow; the pressure required to drive unit outflow increased 4.4-fold between 5 and 20 cmH(2)O. The increased opposition to outflow at 20 cmH(2)O was equivalent to an effective osmotic pressure of 13-17 cmH(2)O at the interface. Since the infusate's osmotic pressure was only 0.9 cmH(2)O, this implied concentration polarization to 15-18 g l(-1) hyaluronan at the interface. 5. Mechanical perforation of the lining, or enzymatic degradation of the interstitial matrix by chymopapain, abolished the quasi-plateau. Hydrational expansion of the matrix by similar to 2-fold did not. The increased opposition to outflow was reversible by washing out the hyaluronan, or by reducing P-j. It was unaffected by interruption of tissue blood flow or synoviocyte oxidative metabolism. These properties are compatible with a concentration polarization mechanism, i.e. flow-induced concentration of hyaluronan at the synovial interface due to molecular reflection. 6. A concentration polarization theory was developed for a partially reflected solute. Numerical solutions supported the feasibility of this osmotic explanation of the quasi-plateau. Additional mechanisms may also be involved. 7. It is concluded that native-size hyaluronan helps to retain synovial fluid in the joint cavity when pressure is raised and acts, at least in part, by exerting osmotic pressure at the interface between synovial matrix and a concentration polarization layer.