Respiratory gases of synovial fluids

Increased hyperpolarized [1‐13C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C‐labelled bicarbonate

“…Leukocytes become increasingly glycolytic on activation as do stromal cells, such as fibroblast‐like synoviocytes in RA 49. Increased glycolysis is consistent with previous studies that have shown this more directly, for example, synovial fluid taken from patients with RA has shown elevated lactate levels 9, 12, 13…”

“…The inflammatory milieu contains many mediators, including protons, and early measurements of synovial fluid pH from rheumatoid arthritis (RA) patients found a pH of 7.21, compared with 7.43 in healthy subjects 8. Similar acidosis was observed by others,9, 10 with a fourth study showing that RA synovial fluid can become very acidic (pH 6.61 versus pH 7.30) 11. However, a more recent study found that, although RA synovial fluid was more acidic than that of synovial fluid from osteoarthritis (OA) patients, neither was acidic (RA pH ~ 7.5 and OA pH ~ 7.65) 12.…”

“…This enormous increase in sensitivity has enabled real‐time imaging of tissue metabolism in vivo following intravenous injection of hyperpolarized 13 C‐labelled substrates,36 including in humans 37, 38. Previous magnetic resonance spectroscopic imaging (MRSI) studies in rats injected with hyperpolarized [1‐ 13 C]pyruvate showed raised lactate‐to‐pyruvate ratios in CFA‐induced inflammation,39 which, considering the relationship observed between lactic acid and acidosis,9, 12, 13 suggested that acidosis must occur in this widely used model. The aim of this study was to determine if tissue acidosis actually does occur in regions where there was increased lactate labelling by using hyperpolarized [ 13 C]bicarbonate to measure tissue extracellular pH 40, 41…”

“…Although there have been several reports of tissue acidosis occurring in RA,8, 9, 10, 11 there is large individual variability 9, 12. In mouse models of arthritis it is often assumed that tissue acidosis occurs, but no data exists to substantiate this belief.…”

“…Moreover, the reported pH range shows clear individual variation: pH ~ 6.84‐7.43,9 and pH ~ 6.95‐7.75,12 suggesting that acidosis is not necessarily a common feature of arthritis. Several studies have found a correlation between synovial lactate concentration and acidosis,9, 12, 13 and it has been suggested that acidosis results from inflammation, where glucose is metabolized to pyruvate and then to lactic acid under the relatively anaerobic conditions of arthritic synovial fluid, where low pH and lactic acid concentrations correlate with low O 2 concentration 9, 10, 14…”