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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR032811-09A1
Application #
3156418
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1983-07-01
Project End
1995-07-31
Budget Start
1992-08-15
Budget End
1993-07-31
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Simkin, P A; Bassett, J E (1995) Cartilage matrix molecules in serum and synovial fluid. Curr Opin Rheumatol 7:346-51
Simkin, P A (1995) Why this joint and why not that joint? Scand J Rheumatol Suppl 101:13-6
Simkin, P A (1995) Synovial perfusion and synovial fluid solutes. Ann Rheum Dis 54:424-8
Simkin, P A; Bassett, J E; Lee, Q P (1994) Not water, but formalin, dissolves urate crystals in tophaceous tissue samples. J Rheumatol 21:2320-1
Simkin, P A; Wu, M P; Foster, D M (1993) Articular pharmacokinetics of protein-bound antirheumatic agents. Clin Pharmacokinet 25:342-50
Bassett, J E; Simkin, P A; Jacobs, C et al. (1992) Avoidance of endotoxin-induced inflammation during studies of albumin clearance from caprine joints. Exp Physiol 77:839-48
Weinberger, A; Simkin, P A (1989) Plasma proteins in synovial fluids of normal human joints. Semin Arthritis Rheum 19:66-76
Stone, G C; Wall, B A; Oppliger, I R et al. (1989) A vasculopathy with deposition of lambda light chain crystals. Ann Intern Med 110:275-8
Downey, D J; Simkin, P A; Taggart, R (1988) The effect of compressive loading on intraosseous pressure in the femoral head in vitro. J Bone Joint Surg Am 70:871-7
Simkin, P A; Downey, D J; Kilcoyne, R F (1988) Apophyseal arthritis limits lumbar motion in patients with ankylosing spondylitis. Arthritis Rheum 31:798-802

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