Hong M K, Kent K M, Mehran R, Mintz G S, Tio F O, Foegh M, Wong S C, Cathapermal S S, Leon M B
Department of Internal Medicine (Cardiology Division) of the Washington (DC) Hospital Center, Washington, DC, USA.
Circulation. 1997 Jan 21;95(2):449-54. doi: 10.1161/01.cir.95.2.449.
In-stent restenosis results primarily from neointimal hyperplasia. This study evaluated the efficacy and the optimal mode of administration of angiopeptin, a somatostatin analogue with antiproliferative activity, in a porcine coronary in-stent restenosis model.
Forty pigs were randomly assigned to one of four groups (n = 10 per group): (1) controls receiving saline infusion at the site of stent implantation via a local delivery catheter, (2) local treatment group receiving one-time treatment (200 (micrograms angiopeptin) at the site of stent placement, (3) systemic treatment group receiving continuous angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 micrograms/kg total dose) and (4) combined local and systemic treatment group. Then, one oversized Palmaz-Schatz stent (mean ratio of stent to artery diameters, 1.3:1) was implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal percent diameter stenosis), intravascular ultrasound (total in-stent neointimal volume), and histology (maximal area stenosis). Systemic treatment produced the least neointimal hyperplasia and significantly reduced in-stent restenosis compared with the control group by all end points, despite similar degrees of injury. Angiography showed 25 +/- 17% versus 50 +/- 17% diameter stenosis in the systemic angiopeptin group versus the control group (P < .0001), intravascular ultrasound revealed 23 +/- 10 versus 58 +/- 27 mm3 neointimal volume in the systemic angiopeptin versus control group (P = .0002), and histology showed 41 +/- 16% versus 69 +/- 18% area stenosis (P = .0016) in the systemic angiopeptin versus control group. Plasma angiopeptin levels revealed rapid clearance (within 6 hours) after local therapy, whereas the levels persisted for up to 2 weeks in the systemic group.
This study shows that continuous subcutaneous treatment with angiopeptin after stent implantation significantly reduces in-stent restenosis by inhibiting neointimal hyperplasia.
支架内再狭窄主要由新生内膜增生引起。本研究在猪冠状动脉支架内再狭窄模型中评估了血管肽素（一种具有抗增殖活性的生长抑素类似物）的疗效及最佳给药方式。
40头猪被随机分为四组（每组n = 10）：（1）对照组，通过局部递送导管在支架植入部位输注生理盐水；（2）局部治疗组，在支架置入部位一次性给予血管肽素200微克；（3）全身治疗组，通过皮下渗透泵在1周内持续给予血管肽素（总剂量200微克/千克）；（4）局部与全身联合治疗组。然后，在左前降支冠状动脉植入一枚超大的帕尔马兹-施查茨支架（支架与动脉直径的平均比例为1.3:1）。4周后通过血管造影（最大直径狭窄百分比）、血管内超声（支架内新生内膜总体积）和组织学（最大面积狭窄）评估新生内膜反应程度。全身治疗产生的新生内膜增生最少，与对照组相比，所有终点指标均显著降低支架内再狭窄，尽管损伤程度相似。血管造影显示，全身血管肽素组与对照组的直径狭窄分别为25±17%和50±17%（P <.0001）；血管内超声显示，全身血管肽素组与对照组的新生内膜体积分别为23±10和58±27立方毫米（P =.0002）；组织学显示，全身血管肽素组与对照组的面积狭窄分别为41±16%和69±18%（P =.0016）。血浆血管肽素水平显示，局部治疗后迅速清除（6小时内），而全身治疗组的水平可持续长达2周。
本研究表明，支架植入后持续皮下给予血管肽素可通过抑制新生内膜增生显著降低支架内再狭窄。
