水蛭素对兔动脉粥样硬化股动脉球囊血管成形术后再狭窄的抑制作用。

Effectiveness of hirulog in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.

作者信息

Sarembock I J, Gertz S D, Thome L M, McCoy K W, Ragosta M, Powers E R, Maraganore J M, Gimple L W

机构信息

Department of Medicine, University of Virginia, Charlottesville 22908, USA.

出版信息

J Vasc Res. 1996 Jul-Aug;33(4):308-14. doi: 10.1159/000159158.

DOI:10.1159/000159158

PMID:8695755

Abstract

BACKGROUND

Thrombin may play an important role in restenosis after balloon angioplasty (BA). Angiographic and pathologic restenosis have been shown to be reduced after BA in an atherosclerotic rabbit model using recombinant desulfatohirudin, a selective and direct thrombin inhibitor. We hypothesized that potent and specific thrombin inhibition with the synthetic peptide hirulog given intravenously at the time of angioplasty would reduce restenosis in rabbits, confirming a specific role of thrombin in restenosis.

METHODS AND RESULTS

Focal femoral atherosclerosis was induced in 27 rabbits by air desiccation endothelial injury followed by a 2% cholesterol diet for 1 month. Rabbits received either heparin (150 units/kg bolus, n = 14) or hirulog (5 mg/kg bolus followed by 5 mg/kg/h for 2 h, n = 13) at the time of BA (2.5-mm balloon with three 60-second, 10-atm inflations 60 s apart). Angiograms performed before and after BA and before sacrifice were analyzed quantitatively. Rabbits were sacrificed 28 days after BA for quantitative histopathologic analysis. Minimum luminal diameter (mm) did not differ between treatment groups before (1.1 +/- 0.2 vs. 1.2 +/- 0.1 mm) or after (1.5 +/- 0.2 vs. 1.6 +/- 0.1) BA in arteries from heparin-versus hirulog-treated rabbits, respectively. At 28 days, however, minimum luminal diameter was significantly less (1.0 +/- 0.4 vs. 1.5 +/- 0.2, p = 0.0001) and percent stenosis was greater (0.46 +/- 0.25 vs. 0.22 +/- 0.08, p = 0.0002) in arteries from heparin- versus hirulog-treated rabbits, respectively. Similarly, quantitative histopathology showed less cross-sectional area narrowing by plaque in the hirulog group (56 +/- 24 vs. 42 +/- 21%, p = 0.04).

CONCLUSION

A 2-hour infusion of hirulog at the time of angioplasty improved late angiographic luminal dimensions and reduced cross-sectional area narrowing by plaque in rabbits compared with heparin controls. Together with previous studies, this confirms a specific role for thrombin in restenosis after angioplasty.

摘要

背景

凝血酶可能在球囊血管成形术（BA）后再狭窄中起重要作用。在使用重组去硫酸水蛭素（一种选择性直接凝血酶抑制剂）的动脉粥样硬化兔模型中，已表明BA后血管造影和病理再狭窄有所减少。我们推测，在血管成形术时静脉注射合成肽水蛭素进行有效且特异性的凝血酶抑制，会减少兔的再狭窄，从而证实凝血酶在再狭窄中的特定作用。

方法与结果

通过空气干燥内皮损伤，然后给予2%胆固醇饮食1个月，在27只兔中诱导局灶性股动脉粥样硬化。在BA时（使用2.5毫米球囊，分三次60秒、10个大气压充气，每次充气间隔60秒），兔分别接受肝素（150单位/千克推注，n = 14）或水蛭素（5毫克/千克推注，随后以5毫克/千克/小时持续2小时，n = 13）。对BA前后及处死前的血管造影进行定量分析。BA后28天处死兔进行定量组织病理学分析。在肝素治疗组与水蛭素治疗组兔的动脉中，BA前最小管腔直径（毫米）无差异（分别为1.1±0.2对1.2±0.1毫米），BA后也无差异（分别为1.5±0.2对1.6±0.1）。然而，在28天时，肝素治疗组兔动脉的最小管腔直径明显更小（1.0±0.4对1.5±0.2，p = 0.0001），狭窄百分比更高（0.46±0.25对0.22±0.08，p = 0.0002）。同样，定量组织病理学显示水蛭素组斑块导致的横截面积狭窄更小（56±24对42±21%，p = 0.04）。