Drugs in Reducing the Development of Rat Intimal Hyperplasia after Endothelial Denudatiotn

Jung, Suk In; Cho, Min Young; Kim, Young Sik; Yeom, Bom Woo; Whang, Cheung Wung

Abstract

Intimal hyperplasia is the universal response to endothelial denudation and occur after a variety of vascular procedures. In a proportion of cases the smooth muscle cell proliferation may lead to stenosis of the blood vessels. The precise pathophysiologic pathways leading to the development of intimal hyperplasia have not been characterized. Once the surface has been denuded of endothelium, a stereotyped sequence of events ensues and leads to intimal thickening. The denuded regions are immediately covered by a carpet of platelets. SMC in the media begin to proliferate. They then migrate into the intima and continue to proliferate as well as to synthesize and secrete large amounts of extracellular matrix. This study was undertaken to examine the effect of drugs on the development of proliferative intimal lesion after experimental arterial injury in a rat model. Aortic denudation was performed by balloon catheter in 30 rats. The rats were divided into five group: control group, normal feeding; heparin group, heparin 1200 U/kg/day subcutaneously; steroid group, dexamethasone 0.1 mg/kg/day; CsA group, CsA 3 mg/kg/day subcutaneously; ACE inhibitor, ramipril 10 mg/kg/day subcutaneously. The rat were sacrified and aortas were perfused and fixed at 21 days after denudation. Microscopic findings were observed and cross sectional intima-to-media ratio were calculated. The results were as follows: 1) Normal aorta with intima to media ratio was 0.38+/-0.06 2) Marked intimal thickening with a mean I-M ratio of 1.35+/-0.45 in the control group. 3) In contrast, the I-M ratio in the heparin group was 0.54+/-0.23, steroid group was 0.48+/-0.21, CsA group was 0.64+/-0.12, ramipril group was 0.71+/-0.27(P<0.05). In summary, this study shows that repair in even the simplest model of vascular injury is an exceedingly complex process and further studies are required.