To quantify extracellular adenosine triphosphate (ATP) levels in human platelet-poor plasma as a potential source of synovial fluid ATP, and to determine variables affecting these levels.
ATP was measured by the specific luciferase method; platelet beta thromboglobulin was determined by radioimmunoassay. The effects of fasting, feeding, venipuncture, and muscular exercise were determined by serial venipuncture in healthy subjects. Diurnal variation was determined by serial sampling through indwelling venous catheters in 3 healthy subjects and 3 women with knee osteoarthritis.
Unlike beta thromboglobulin levels, which did not change, an invariable marked (mean 58%) fall in plasma ATP was noted 15 min after the first venipuncture, whether the subject had eaten or not. Indomethacin treatment had no effect on this phenomenon. Exercise of forearm muscles had no effect on plasma ATP. The drop in plasma ATP occurred between 3 and 15 min, with recovery at about 90 min. A diurnal variation in plasma ATP was found with trough levels at noon and at night during sleep.
The predictable sharp fall in plasma ATP levels induced by venipuncture and the clear diurnal variation suggest that plasma contains ATP independent of platelet dense body release and endothelial cell needle trauma. Synovial plasma flow at peak (600 nM) levels is insufficient to provide more than one-third of the extracellular ATP needed to generate inorganic pyrophosphate in articular tissues.