猪冠状动脉内双重抗血小板治疗疗效与支架内新生内膜增生发展之间的关联。
Association between the efficacy of dual antiplatelet therapy and the development of in-stent neointimal hyperplasia in porcine coronary arteries.
作者信息
Hemetsberger Rayyan, Farhan Serdar, Strehblow Christoph, Sperker Wolfgang, Pavo Imre, Petrasi Zsolt, Hemetsberger Hani, Posa Aniko, Huber Kurt, Glogar Dietmar, Gyöngyösi Mariann
机构信息
Department of Cardiology, Medical University of Vienna, Vienna, Austria.
出版信息
Coron Artery Dis. 2008 Dec;19(8):635-43. doi: 10.1097/MCA.0b013e32831425ed.
OBJECTIVE
We set out to compare the effectiveness of platelet aggregation therapy in association with the development of in-stent neointimal hyperplasia in porcine coronary arteries.
METHODS
Thirty-two pigs underwent coronary stenting with bare-metal stents under general anaesthesia. One hundred milligrams of aspirin and loading doses of either 300 mg clopidogrel (group C, n=13) or 2 x 500 mg ticlopidine (group T, n=19) were administered before intervention. During the follow-up, the animals received a daily dose of 100 mg aspirin and 75 mg clopidogrel or 2 x 250 mg ticlopidine, respectively. After 4 weeks, the histopathological and histomorphometric parameters of the explanted stented coronaries were assessed. Levels of circulating cytokines and platelet activation factors were measured. ADP-induced and collagen-induced aggregation was measured immediately before stenting and then every 3rd day. The aggregation profiles were calculated and correlated with the histological parameters.
RESULTS
The fibrin deposition scores and inflammation scores were higher in group T than in group C, with similar injury scores. Endothelialization was complete in both groups. A significantly lower neointimal area (1.08+/-0.36 vs. 1.58+/-0.5, group C vs. T, P=0.026) and percentage of area stenosis (29.8+/-12.1 vs. 44.3+/-16.3, group C vs. T, P=0.032) were observed in group C. The loading dose of clopidogrel significantly reduced the platelet activation parameters before the first angiography as compared with ticlopidone. Clopidogrel treatment resulted in a significantly better aggregation profile relative to ticlopidine (mean ADP-induced aggregation: 28.4+/-9.1 vs. 52.5+/-12.0%, P<0.001). Significant (P<0.05) positive linear correlations were observed between the ADP-induced aggregation profile and the neointimal area (r=0.584), percentage of area stenosis (r=0.666), inflammation (r=0.476) and fibrin deposition (r=0.496).
CONCLUSION
The effectiveness of dual antiplatelet therapy plays an important role in the inhibition of in-stent neointimal hyperplasia.
目的
我们旨在比较血小板聚集疗法与猪冠状动脉支架内新生内膜增生发展的相关性及有效性。
方法
32头猪在全身麻醉下接受裸金属支架冠状动脉支架置入术。干预前给予100毫克阿司匹林及负荷剂量的300毫克氯吡格雷（C组，n = 13）或2×500毫克噻氯匹定（T组，n = 19）。随访期间，动物分别每日接受100毫克阿司匹林和75毫克氯吡格雷或2×250毫克噻氯匹定。4周后，评估取出的带支架冠状动脉的组织病理学和组织形态学参数。测量循环细胞因子和血小板活化因子水平。在支架置入前及之后每3天测量ADP诱导和胶原诱导的聚集。计算聚集曲线并与组织学参数相关联。
结果
T组的纤维蛋白沉积评分和炎症评分高于C组，损伤评分相似。两组内皮化均完成。C组观察到明显更低的新生内膜面积（1.08±0.36对1.58±0.5，C组对T组，P = 0.026）和面积狭窄百分比（29.8±12.1对44.3±16.3，C组对T组，P = 0.032）。与噻氯匹定相比，氯吡格雷的负荷剂量在首次血管造影前显著降低血小板活化参数。相对于噻氯匹定，氯吡格雷治疗导致聚集曲线明显更好（平均ADP诱导聚集：28.4±9.1对52.5±12.0%，P<0.001）。在ADP诱导的聚集曲线与新生内膜面积（r = 0.584）、面积狭窄百分比（r = 0.666）、炎症（r = 0.476）和纤维蛋白沉积（r = 0.496）之间观察到显著（P<0.05）正线性相关。
结论
双联抗血小板治疗的有效性在抑制支架内新生内膜增生中起重要作用。
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