Short-term dexamethasone treatment inhibits vein graft thickening in hypcrcholcstcrolemic ApoE3Leiden transgenic mice

Objective: The aim of this study was to assess whether the anti-inflammatory agent dexamethasone can inhibit vein graft thickening without the occurrence of serious side effects. Methods. Venous interposition grafting was performed in the common carotid artery of hypercholesterolemic ApoE3Leiden transgertic mice. Mice were treated with dexamethasone (0.15 mg . kg(-1) . d(-1) orally), and after 28 days, vein graft thickening was quantified. Results: Treatment with dexamethasone resulted in a significant 43% reduction in lesion area without changes in lesion composition when compared with nontreated controls. However, dexamethasone, when administered for a prolonged period of time, is known for its potentially serious side effects. To overcome these potential side effects of prolonged dexamethasone treatment, the effect of a short-term 7-day dexamethasone treatment was studied. This short dexamethasone treatment resulted in a 49% decrease of vein graft thickening at 28 days. Furthermore, it was demonstrated that dexamethasone treatment led to reduced local expression of several proinflammatory cytokines and factors in the vein grafts 24 hours after surgery. Finally, observations in mice were verified in human saphenous organ cultures. Exposure to dexamethasone for either 7 or 28 days significantly reduced intimal hyperplasia formation on cultured saphenous vein segments. Conclusions. Short-term anti-inflammatory treatment with dexamethasone leads to a significant reduction in vein graft thickening over an extended period, possibly by the reduction of early expression of proinflamniatory cytokines. This 7-day treatment minimizes the risk of unwanted side effects of long-term dexamethasone treatment and may be a new approach to prevent graft failure.