This grant focuses on the microvascular physiology of the synovium both in human subjects with rheumatoid arthritis and in goats with retroviral arthritis. In both species, isotopic tools will be used to determine the rate of synovial plasma flow, the rate of lymphatic drainage, and the microvascular permeability to water and to plasma proteins. Special attention will be paid to microvascular effects of therapy with steroidal and nonsteroidal anti-inflammatory drugs. In particular, it is thought that plasma flow may be prostaglandin-dependent in some subjects and that anti-prostaglandin drugs may therefore promote ischemia. Observations in patients at rest and during passive and active motion will examine the impact of exercise on synovial microvascular function. This aim tests the hypothesis that gentle motion is more beneficial than rest, but sustained work is detrimental to circulatory-metabolic homeostasis in active rheumatoid joints. A new tool for assessment of synovial ischemia, magnetic resonance spectroscopy, will be used to evaluate wrist and hand joints and will be validated by direct intra-articular measurements of pH and temperature. The radioisotopic measures will be used to evaluate both the effects of aging on synovial microvascular function in control goats and the effects of retroviral arthritis in infected animals. These serial studies will follow and quantify the physiology of both the virus-vulnerable carpal joints and the relatively virus-resistant hocks. A course of acute inflammation evolving through an ischemic phase to "burned out" synovitis is expected. The microvascular effects of steroidal and nonsteroidal anti-inflammatory drugs will be quantified at each stage of this evolution.