Inflammatory arthritis, hypoxia and vascularity

We have employed novel technology to investigate the relationship between synovial tissue oxygen levels and vascularity in human inflammatory arthritis. Silver microelectrodes were used to measure synovial tissue oxygen levels in knee joints of 15 patients with inflammatory arthritis (6 RA, 2 SLE, 1 psoriatic, 1 crystal, 2 reactive and 2 seronegative oligo-arthritides). Synovial membrane cells were obtained from tissue biopsies and ex-vivo production of vascular endothelial growth factor (VEGF) was measured. In RA patients, 50 ml N/Saline was injected into the joint and the electrode positioned in the cavity such that the rate of oxygen consumption could be measured. Microelectrodes were also used to assess synovial pO2 levels in a single metacarpophalngeal (MCP) joint in 5 RA patients. These joints were simultaneously imaged by high resolution ultrasound and power colour doppler to determine the relationship between joint architecture, vasculature and tissue pO2.

In knees, synovial tissue pO2 levels were significantly lower in patients with active RA (mean = 7 mm Hg) than in patients without RA (mean = 40 mm Hg; P = 0.002). In RA, oxygen was consumed from N/Saline introduced into the cavity at a rate of 20.5 mm Hg/min. Production of VEGF from synovial cells was greater for patients with RA (mean = 868 pg/106 cells) than from synovial cells from patients without RA (mean = 84 pg/106 cells; P < 0.01).

In the 5 MCP joints studied, a total of 9 vascular areas were sampled. The mean pO2 at these sites was 97 mmHg. In 19 non-vascular areas sampled, the mean pO2 was 34 mm Hg (range 6-73). In a vascular erosion the tissue pO2 was measured as 41 mmHg.

In conclusion, marked hypoxia is observed in selected regions of inflamed synovium and is a likely stimulus for local VEGF production and angiogenesis. However, the increased vascularity associated with erosive damage is insufficient to restore oxygen homeostasis at the site of joint destruction.