Vascular surgical society of great britain and ireland: uptake of tetracycline in aortic aneurysms: influence on inflammation and proteolysis

Abstract

BACKGROUND: Derivatives of tetracycline (TC), through their inhibition of matrix metalloproteinases (MMPs), have been suggested as potential medical therapy to limit growth of abdominal aortic aneurysms (AAAs), but penetration of the aortic wall in vivo has not been demonstrated. The uptake and concentration of TC in aneurysm wall, and its effect on MMP and cytokine production, were investigated. METHODS: Patients undergoing elective AAA repair (n = 5) were given a single bolus of intravenous TC 500 mg on induction of anaesthesia. The TC concentrations achieved in serum, aneurysm wall and mural thrombus were determined using a microbiological assay. In separate patients, not given TC, AAA biopsy explants were established and the effect of TC (0, 10 and 100 &mgr;g ml-1) on hydroxyproline, MMP-9 and cytokine (MCP-1 and interleukin (IL) 6) secretion were investigated using colorimetric assays and immunoassays. RESULTS: At the time of aortic cross-clamping median TC concentration was 9 (range 5-12) &mgr;g ml-1 in serum, 2.7 (1.3-9. 6) &mgr;g g-1 in AAA wall and nil in mural thrombus (see Table ). CONCLUSION: TC rapidly penetrates AAA wall in vivo and inhibits MMP-9 and MCP-1 release by AAA explants. This suggests that TCs have the potential to limit aneurysm growth.