Synovial Cavity Research Articles

Extravasation in the knee induced by antidromic stimulation of articular C fibre afferents of the anaesthetized cat.

Electrical stimulation of the cut distal end of the posterior articular nerve (p.a.n.) of the cat knee joint resulted in significant extravasation of plasma proteins and erythrocytes into the synovial cavity of the knee. This effect was mediated by group IV afferents (C fibres) since stimulation of p.a.n. suprathreshold for group II or III afferents but subthreshold for group IV afferents did not produce extravasation. Unmyelinated sympathetic efferent fibres in the joint nerve did not contribute to the extravasation and were responsible for a diminution of this response as shown by the enhanced extravasation occurring after adrenergic blockade. Plasma and erythrocyte extravasation was mediated by afferents containing substance P (SP), as demonstrated by the reversible abolition of extravasation when the substance P antagonist (D-Pro4,D-Trp7,9,10)-SP (4-11) was injected into the synovial cavity. In some animals it was observed that electrical stimulation of the cut distal end of p.a.n. in one limb resulted in extravasation in the contralateral knee joint. It is suggested that articular C fibre afferents could make a significant neurogenic contribution to the initiation or maintenance of inflammatory joint disease.

Immune complexes in synovial fluid and serum from patients with disseminated gonococcal infection: evidence for local immune complex formation within the joint.

Twenty one patients with acute arthritis associated with disseminated gonococcal infection (DGI) were studied. Synovial fluid (SF) from 14 and serum from 15 (matched in eight) were assayed for the presence of immune complexes (IC) by the Raji cell immunofluorescent assay (Raji IFA) and the 125I-Clq polyethylene glycol (PEG) binding assay. Higher levels and frequency of IC were detected in the SF by both IC assays and these were associated with a significant increase in complexes containing IgM over serum (p less than 0.02). Complexes containing IgG were found predominantly in serum and were infrequent in SF (p less than 0.003). These data suggest that the arthritis of DGI may result from primary immune complex formation within the synovial cavity after local antibody synthesis within the synovium in response to gonococcal seeding.

Is chronic synovitis an example of reperfusion injury?

In an attempt to define why the joint synovial cavity is prone to develop persistent synovial inflammation we show that hypoxia is induced by pressure changes caused by exercise in the presence of an inflammatory effusion. On resting 'reperfusion injury' may take place. The biochemistry of reperfusion injury has only recently been defined and perhaps surprisingly for an insult that has hypoxia as its central ingredient involves the subsequent production of oxygen derived free radical species. We apply the reaction sequences that are believed to occur during hypoxic/reperfusion injury to the joint synovial cavity and, on the basis of reported 'in vivo' observations, suggest novel therapeutic approaches that we believe are applicable to the treatment of persistent synovial inflammation.

Role of Synovial Fluid Cells in the Healing of Flexor Tendons

A 1-cm segment of repaired rabbit flexor tendon was first subjected to 10,000 rads of x-radiation and then placed in the synovial cavity of a rabbit's knee joint. Macroscopic examination revealed healing at the repair site and rounding of the tendon ends without adhesions. Light- and electron-microscopic studies revealed cells resembling fibroblasts at the repair site and the periphery laying down collagen. Healing of this irradiated nonviable tendon was brought about by the cells present in the synovial fluid.

The Use of Carbon Fiber Implants in Anterior Cruciate Ligament Surgery

In cruciate ligament surgery where carbon fibers have been placed within the synovial cavity of the knee joint, an inadequate biologic response occurs that leads to failure of the implant and fragmentation within the joint. This paper describes in detail the operative technique of one surgeon (A.E.S.) of placing a collagen-coated carbon fiber implant through the retrosynovial route of the anterior cruciate ligament. It also describes the clinical and arthroscopic follow-up evaluations of four consecutive cases by an independent surgeon (P.F.). The results confirm the contention that when the carbon fibers are placed either within the remnants of the original ligament or within a sheath of fascia lata and maintained in the retrosynovial situation, no carbon debris appears within the joint cavity, and a normal-looking cruciate ligament results.

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

A synovial cavity is separated from plasma by synovial intima in series with capillary endothelium. Because 20% of the intimal surface is bare interstitium, the system is a convenient model for the study of passive transport through serial endothelial and interstitial layers. Here hydraulic flow across the composite barrier was investigated in forty-seven knees of isolated, blood-perfused rabbit hindquarters, at intra-articular pressures between 4 and 30 cmH2O. In order to measure barrier conductance at constant intra-articular pressure, pressure on the opposite side of the barrier was varied, i.e. capillary blood pressure (PC). Capillary pressure was changed by alteration of vascular perfusion pressures, and the resulting changes in rate of absorption of Krebs solution from the synovial cavity (QS) were recorded. Trans-synovial absorption was a negative linear function of PC at each joint pressure, in verification of the applicability of Starling's hypothesis to this system. The hydraulic conductance of the blood-joint barrier was calculated as dQS/dPC. Conductance was independent of intra-articular pressure below 9 cmH2O and was 0.12 +/- 0.015 microliter min-1 mmHg-1 (mean +/- S.E. of mean). Barrier conductance increased as a curvilinear function of intra-articular pressure above 9.4 cmH2O (yield pressure). At 30 cmH2O conductance averaged 0.60 +/- 0.06 microliter min-1 mmHg-1, a 5-fold increase. A hyperbolic curve relating net barrier conductance to joint pressure was predicted from the hypothesis that interstitial conductance increases as a monotonic function of intra-articular pressure above yield pressure (Appendix). The data were in reasonable agreement with the theoretical hyperbola. Interstitial conductivity (3 X 10(-7)-7 X 10(-7) cm4 s-1 N-1 below yield pressure) and mean endothelial conductance (1.1 X 10(-4)-1.4 X 10(-4) cm3 s-1 N-1) were evaluated and compared with values in other tissues. Synovial endothelium contains on average 0.25 fenestrae micron-1 circumference. The conductance of a single fenestra was calculated to be 2.3 X 10(-13) cm5 s-1 N-1. Interstitial resistance accounted for roughly half the total resistance below yield point: therefore dQS/dPC should not be equated with 'capillary filtration capacity' in tissues with dense or fenestrated capillary beds. Large inconsistencies between interstitial conductivity and glycosaminoglycan concentration are noted, and mechanistic explanations of increases in conductivity with joint pressure are offered.

Baker's cyst. Radionuclide arthrographic findings.

Radionuclide arthrography of the knee is described using Tc-99m sulfur colloid, which is injected into the synovial cavity following partial distension of the joint space with saline. The preliminary findings in Baker's cyst are described. There appear to be four patterns: 1) a herniation or cyst that can be posterior, inferior, medial or lateral to the knee synovial space; 2) a limited leak inferiorly toward the calf or superiorly toward the thigh; 3) extensive leak: giant cyst found in patients with rheumatoid arthritis; 4) multiple "cysts" or communications with the knee synovial space. The series is small, and more work is needed before these preliminary findings can be used as firm categories. Radionuclide arthrography should be considered in patients with unexplained calf pain or pain behind the knee, especially with a history of previous internal knee derangement, or rheumatoid arthritis in whom ruptured cysts can closely mimic acute thrombophlebitis. Radionuclide arthrography has certain advantages over contrast arthrography and also arthroscopy in the diagnosis of Baker's cyst.

Clinical pharmacokinetics of the salicylates.

The use of salicylates in rheumatic diseases has been established for over 100 years. The more recent recognition of their modification of platelet and endothelial cell function has lead to their use in other areas of medicine. Aspirin (acetylsalicylic acid) is still the most commonly used salicylate. After oral administration as an aqueous solution aspirin is rapidly absorbed at the low pH of the stomach millieu. Less rapid absorption is observed with other formulations due to the rate limiting step of tablet disintegration - this latter factor being maximal in alkaline pH. The rate of aspirin absorption is dependent not only on the formulation but also on the rate of gastric emptying. Aspirin absorption follows first-order kinetics with an absorption half-life ranging from 5 to 16 minutes. Hydrolysis of aspirin to salicylic acid by nonspecific esterases occurs in the liver and, to a lesser extent, the stomach so that only 68% of the dose reaches the systemic circulation as aspirin. Both aspirin and salicylic acid are bound to serum albumin (aspirin being capable of irreversibly acetylating many proteins), and both are distributed in the synovial cavity, central nervous system, and saliva. The serum half-life of aspirin is approximately 20 minutes. The fall in aspirin concentration is associated with a rapid rise in salicylic acid concentration. Salicylic acid is renally excreted in part unchanged and the rate of elimination is influenced by urinary pH, the presence of organic acids, and the urinary flow rate. Metabolism of salicylic acid occurs through glucuronide formation (to produce salicyluric acid), and salicyl phenolic glucoronide), conjugation with glycine (to produce salicyluric acid), and oxidation to gentisic acid. The rate of formation of salicyl phenolic glucuronide and salicyluric acid are easily saturated at low salicylic acid concentrations and their formation is described by Michaelis-Menten kinetics. The other metabolic products follow first-order kinetics. The serum half-life of salicylic acid is dose-dependent; thus, the larger the dose employed, the longer it will take to reach steady-state. There is also evidence that enzyme induction of salicyluric acid formation occurs. No significant differences exist between the pharmacokinetics of the salicylates in the elderly or in children when compared with young adults. Apart from differences in free versus albumin-bound salicylate in various disease states and physiological conditions associated with low serum albumin, pharmacokinetic parameters in patients with rheumatoid arthritis, osteoarthritis, chronic renal failure or liver disease are essentially the same.(ABSTRACT TRUNCATED AT 400 WORDS)

An assay for estimating the cytotoxicity of synovial fluid from patients with rheumatoid arthritis.

The joint is the prime site of involvement in rheumatoid arthritis: the synovium showing lymphocytic involvement and damage. The synovial fluid shows evidence of inflammation such as increased neutrophils and raised CRP. Application of a cell-free extract of serum or synovial fluid from patients with rheumatoid arthritis, or serum from normal individuals on to 111indium oxine radiolabelled endothelial cells and fibroblasts, promotes the release of the isotope as a result of cell damage and death (cytotoxicity). In paired samples, synovial fluid was consistently more cytotoxic than rheumatoid serum. There was no difference in the cytotoxicity of rheumatoid serum or normal serum. These results demonstrate the presence of soluble factors in synovial fluid, which are capable of destroying cells, typical of those found in the synovial cavity, in blood vessels and in connective tissue generally. This system may prove to be a useful model of inflammatory damage.

A sequential study of virus expression in retrovirus-induced arthritis of goats.

Persistent infection by the retrovirus caprine arthritis--encephalitis virus (CAEV) induces arthritis in goats which closely resembles rheumatoid arthritis. To examine the relationship between virus expression and development of clinical disease, ten goat kids were inoculated with CAEV and examined at successive intervals through 18 months post-infection. Virus was monitored in cell-free synovial fluid cells, serum and peripheral blood cells by titration, co-cultivation and immunofluorescent techniques. Virus was readily recovered from the synovial cavity of all animals during the first 4 weeks of infection, followed by a reduction and fluctuation in virus titres and ability to detect virus. Recovery of CAEV from peripheral blood cells occurred at low frequency while viraemia was rare. Results obtained over a period of 18 months indicate a positive association between virus expression in the synovial cavity and development of clinically detectable disease.

Effects of local administration of hydrocortisone on cartilage degradation in vivo.

The effect of corticosteroid on autologous minced cartilage transplanted into facsimile synovial cavities has been studied. The soluble form of hydrocortisone, as the sodium succinate, reduced proteoglycan loss from cartilage in a dose-dependent manner. In contrast, insoluble hydrocortisone acetate, if given directly into the cartilage-containing cavity, enhanced proteoglycan loss. Injection of the same dose of drug into the inflamed lining tissue reversed this effect. These findings suggest that intra-articular steroid injection may enhance cartilage damage if insoluble preparations are used, but that this may be overcome by injecting into the inflamed lining tissue rather than into the cavity itself.

Morphometry of the ultrastructure of the blood-joint barrier in the rabbit knee.

The ultrastructure of the barrier to water and solute exchange between blood and a synovial cavity was studied morphometrically in five rabbit knees. The synovial surface consisted of 80% synoviocytes and 20% interstitium in direct contact with synovial fluid. The surface intercellular gaps were wide (0.1-5.5 microns). A rich network of capillaries lay just beneath the surface, the commonest (modal) depth of the capillary perimeter being 5 microns at its nearest point. Of these capillaries, 91% were fenestrated in adipose synovium, 44% in areolar synovium and 21% in posterior synovium; the remainder were continuous capillaries. The number of fenestrae per fenestrated capillary was low (approximately 0.5 micron-1, circumference: approximately 6 microns-2). The fenestrae (width 52 nm; membrane thickness 3-4 nm) occupied approximately 1% of the fenestrated endothelial surface-area. Nuclear segments and intercellular junctions were roughly twice as frequent in continuous capillaries as in fenestrated capillaries of the same circumference, indicating that continuous endothelial cells are of smaller surface area than fenestrated cells. The basement membranes of continuous and fenestrated synovial capillaries were relatively thick (98 and 110 nm respectively), perhaps supporting the synovial endothelium during joint motion. In both fenestrated and continuous capillaries the nuclei were preferentially oriented away from the synovial surface (92 and 67% respectively), which presumably facilitates exchange with the surface.

The influence of blood pressure on trans-synovial flow in the rabbit.

Fluid exchange across the synovium lining the cavity of extended knees was studied in twenty rabbit hindquarters. The isolated hindquarters were perfused with blood from an extracorporeal pump-oxygenator system at controlled arterial pressure (PA) and venous pressure (PV). Intra-articular pressure (PJ) was set at 18 cmH2O in most experiments. The rate of trans-synovial absorption of Krebs solution (QS), measured by a drop-counter, was a negative linear function of PA (70-160 mmHg) and of PV (2-42 cmH2O). The sensitivity of exchange to venous pressure ( dQS / dPV , mean -0.25 +/- 0.03 microliter min-1 mmHg-1) was greater than its sensitivity to arterial pressure ( dQS /dPA, mean -0.17 +/- 0.02 microliter min-1 mmHg-1). The ratio of the slopes, ( dQS / dPV )/( dQS /dPA), indicated the pre- to post-capillary vascular resistance ratio. From this ratio and PA, PV, synovial capillary pressures PC were calculated by the equation of Pappenheimer & Soto - Rivera (1948). Trans-synovial absorption rate was a negative linear function of PC. This observation supports the application to the synovial cavity of Starling's hypothesis for fluid exchange between interstitial spaces and plasma (Starling, 1896). The slope dQS /dPC equalled the net hydraulic conductance of the blood-joint barrier (synovium plus capillary endothelium), and averaged -0.425 +/- 0.025 microliter min-1 mmHg-1 at PJ = 18 cmH2O. When PJ was subatmospheric, as is common in extended normal joints, fluid exchange (measured indirectly as dPJ /dt) was only approximately 1/4 as sensitive to blood pressure as at PJ = 18 cmH2O. This observation supported the view that the conductance of the blood-joint barrier depends on PJ.

The density and distribution of capillaries around a synovial cavity.

The interpretation of trans-synovial fluxes requires a knowledge of the number of capillaries present around the joint cavity, and their depths below the surface of the joint lining. Measurements of capillary numbers, depths and dimensions were therefore carried out by light microscopy on synovial tissue sections from five rabbit knees. In addition the surface area of synovial tissue lining the joint was estimated, and the thickness of the synovium measured. Synovial capillary density was found to be uneven, with respect to both anatomical location in the joint cavity and depth below the synovial surface. The large area of synovium over areolar or adipose tissue was highly vascular (67000-83000 capillaries X cm-2 section; mean intercapillary distance 35-55 micron; 228-329 cm2 endothelium X cm-3 synovium). The small area of synovium over tendons was of very low vascularity (2000 capillaries X cm-2 section). From these data and a previous estimate of net filtration capacity, mean synovial endothelial conductivity was estimated as approximately 16 X 10(-7) cm X s-1 X mmHg-1. The depth distribution of the capillaries was extremely skewed, with a sharp peak at 6-11 micron depth. The rapid decay in capillary density at depths greater than 6-11 micron was partly due to an uneven density of capillaries within the synovium itself; and partly due to a lower density in subsynovial tissues. It was concluded that most synovium has a rich capillary bed which is very superficially located and that the depth of periarticular tissue which is effective in exchange processes with the joint cavity is less than 25 microns.

Neutrophil migration in response to chemotactic factors: effects of generation conditions and chemotherapeutic agents.

The effects of various chemotactic factor generation conditions and several chemotherapeutic agents on neutrophil migration were determined using in vitro assay systems designed as models for inflammatory processes occurring in the synovial cavities of patients with rheumatoid arthritis. The microtubule-promoting agent concanavalin A and the microfilament-disrupting agent cytochalasin B were shown in these systems to inhibit neutrophil migration towards zymosan-activated serum-derived chemotactic factors. Neutrophils, immunoglobulin G aggregates, and serum were required for maximum generation of comparable chemotactic factors. Insoluble immunoglobulin G aggregates with or without rheumatoid factor produced more chemotactic factor activity on interaction with neutrophils than soluble immunoglobulin G aggregates. Exposure of neutrophils to supratherapeutic levels of the nonsteroidal antiinflammatory agent aspirin decreased neutrophil response to chemotactic factors while exposure to the slow-acting or immunomodulating agents gold, D-penicillamine, or azathioprine had no effect on this neutrophil function. In vitro systems employing neutrophils, insoluble aggregates, and serum may offer useful means for assaying drug effects on important functional components of the rheumatoid inflammatory process.

Concentrations of some antibiotics in synovial fluid after oral administration, with special reference to antistaphylococcal activity.

One of 4 antibiotics with antistaphylococcal activity was given in a conventional oral dose for one day to each of 20 hospitalised patients with synovial effusion of a knee joint requiring aspiration. Serial synchronous samples of serum and synovial fluid (SF) were taken over 36 hours through indwelling cannulae. No morbidity was experienced either during or after this procedure. Satisfactory antistaphylococcal concentrations in SF were achieved with sodium fusidate (500 mg 8 hourly) and amoxycillin (250 mg 8 hourly). Cephradine (500 mg 6 hourly) frequently failed to reach the minimum inhibitory concentration for Staphylococcus aureus in the SF, and flucloxacillin (250 mg 6 hourly) was unpredictable in its penetration of the synovial space. Wide interpatient variation of both serum and SF concentrations was found. Our results indicate that sodium fusidate is an appropriate early treatment for a nonresistant staphylococcal joint infection. Amoxycillin is a suitable alternative or second antistaphylococcal drug and would also be appropriate initial therapy when the infecting organism is unknown. We strongly recommend that SF antibiotic concentrations be measured, to ensure adequate penetration of the synovial cavity, in the treatment of septic arthritis.

Time-dependence of the pressure-volume relationship in the synovial cavity of the rabbit knee.

The pressure-volume curve of the synovial cavity of the rabbit knee has been determined by the infusion of a non-absorbable oil into the joint space. Pressure (greater than 3 cm H2O) at a given volume decayed as a curvilinear function of time. In consequence, a plot of volume against pressure immediately after a volume increment (the immediate compliance curve) was steeper than a plot of volume against pressure after 5-20 min (the delayed compliance curve) above atmospheric pressure. Similarly, the compliance curve for a rapidly expanded joint was steeper than the compliance curve for the opposite, slowly expanded joint. Observations 2 and 3 indicated that the joint investment was visco-elastic. Pressure at a given volume during aspiration of the expanded joint was always less than pressure at the same volume during infusion. This hysteresis was substantial, the mean energy dissipation being about 37%. Pressure at a given volume increased as a function of time during aspiration, but the pressure recovery was less pronounced than pressure decay during infusion. When the cycle of infusion and aspiration was repeated, the pressure-volume hysteresis loop was displaced progressively towards the volume axis. Observations 5 and 6 were attributed to plasticity of the joint investment. It is concluded that intra-articular pressure at a given volume depends on the rate of change of volume, the direction of change, and the previous history of the joint. The relevance of these properties to fluid dynamics in other interstitial compartments, in arthritic human joints, and to the neurophysiology of mechanoreceptors in the joint investment is discussed.

Distribution of immunoreactive fibronectin and collagen (type I, III, IV) in mouse joints. Fibronectin, an essential component of the synovial cavity border.

Hyaluronic acid traditionally has been held to play a major role in the control of transsynovial exchanges and in the biomechanical properties of synovial fluid and cartilage surfaces. As with previous ultrastructural observations, immunohistochemical data show that a more complex differentiation must be envisaged for interstitial tissues bordering the synovial cavity. In particular, the elective concentration of fibronectin in the lining layer of the synovial membrane and its presence as a fine layer at the articular cartilage surfaces indicate that this glycoprotein, along with hyaluronic acid, may play an important role in joint physiology. Only immunoreactivity for type III procollagen is diffusely distributed in the entire synovial membrane and, in addition, is found associated with fibronectin immunoreactivity at the articular cartilage surfaces.

Physiological compartmentation of fluid within the synovial cavity of the rabbit knee.

1. The relationship between pressure in the suprapatellar region (Psp) of the synovial cavity of the rabbit knee, and volume of fluid (oil or saline) infused into that region displayed a pressure plateau (15 . 5 cm H2O) between 1 . 2 and 2 . 0 ml. 2. No pressure plateau occurred when fluid was infused simultaneously into the suprapatellar and posteromedial regions of the synovial space. 3. Pressure in the posteromedial region (Ppm) did not respond to suprapatellar fluid infusions until onset of the suprapatellar pressure plateau. During the plateau phase, Ppm rose steadily towards Psp. At the end of the plateau phase the two pressures were almost equal and rose in parallel. 4. The plateau phenomen also occurred during aspiration of volume-expanded joints; and was present at all joint angles. 5. It was concluded that the joint space, although anatomically continuous, is divided into two hydraulically separate compartments at physiological pressures. 6. The sites of communication between the two compartments at pathological pressures were explored by casts of the synovial cavity.

Pressure-volume relationships above and below atmospheric pressure in the synovial cavity of the rabbit knee.

1. The pressure-volume relationship in the synovial cavity of the rabbit knee was investigated by the infusion of a non-absorbable oil into the cavity. 2. The pressure (P)-volume (V) curve was sigmoid. Its slope dP/dV (elastance) was steep at subatmospheric, physiological pressures, least steep at 5 cm H2O, and steepened progressively at higher, pathological pressures. 3. Elastance dP/dV was a good approximation to linear functions of P below atmospheric pressure and above 5 cm H2O. Each part of the pressure-volume relationship could therefore be described by an exponential expression. 4. Flexion of the joint increased pressure at a given volume. This was mainly due to steepening of the pressure-volume curve, and also partly due to a shift towards the pressure axis. 5. Pressure-volume curves determined by the infusion of normal saline or Krebs solution were grossly distorted, because these fluids were absorbed across the permeable synovium. 6. The physiological significance of the synovial pressure-volume curve is discussed, and mechanical explanations of the curve are suggested.