Intimal Hyperplasia in a Rat Model after Balloon Induced Arterial Injury

Jung, Sang Hun; Kwun, Woo Hyung; Suh, Bo Yang; Kwun, Koing Bo; Kim, Yong Jin

Abstract

PURPOSE: Intimal hyperplasia is an exaggerated proliferating response to arterial injury and can lead to occlusion and thromboses of arteries and bypass graft following arterial surgery or angioplasty. Medial smooth muscle cell activation has been implicated as the final common pathway leading to the development of intimal hyperplasia. Therefore, therapeutic agents that inhibit vascular smooth muscle cell proliferation should be selected to prevent restenosis. Recent laboratory data suggest that heparin and glucocorticosteroid have antiproliferative effects on smooth cells. We studied the effect of dexamethasone and low molecular weight heparin (LMWH: fragmin) on the suppression of intimal hyperplasia after balloon induced arterial injury in a rat model. METHOD: Twenty five rats were underwent aortic intimal denuation with 2F balloon catheter. The rats were divided into four groups: normal control group (sham operation), control group (experimental group without medication), dexamethasone treatment group (experimental group with intramuscular injection of dexamethasone) and fragmin treatment group (experimental group with subcutaneous injection of 60 IU/kg of LMWH (fragmin(R)). The dexamethasone treatment group was divided into 3 subgroups by graded doses of dexamethasone: subgroup 1, 2 and 3 were injected 0.05 mg/kg, 0.10 mg/kg and 0.15 mg/kg of dexamethasone respectively. Injection of drugs were started 1 days before the intimal injury and continued for 4 weeks, dexamethasone were injected six times a week and fragmin injected daily. The aorta were harvested at 6 weeks after injury. Microscopic examination and cross sectional intima to media height ratio (IMHR) were evaluated. RESULT: All treatment groups showed significant suppression of intimal hyperplasia compare to the control group (P<0.05). Mean IMHR were 0.69+/-0.15 in the control group, 0.39+/-0.11, 0.31+/-0.15 and 0.29+/-0.09 in dexamethasone treatment subgroup 1, 2 and 3 respectively, and 0.39+/-0.14 in fragmin treatment group. There were no statistical difference in dexamethasone treatment subgroups.
CONCLUSION
Dexamethasone and LMWH were effective in suppression of the intimal hyperplasia to an intimal injury in a rat model. In addition, the minimal effective dose of dexamethasone that required to achieve the suppression of intimal hyperplasia is 0.05 mg/kg in this study.