Chen C, Hanson S R, Keefer L K, Saavedra J E, Davies K M, Hutsell T C, Hughes J D, Ku D N, Lumsden A B
Department of Surgery, Veterans Affairs Medical Center, Decatur, Georgia 30033, USA.
J Surg Res. 1997 Jan;67(1):26-32. doi: 10.1006/jsre.1996.4915.
To evaluate the direct effect of nitric oxide (NO) on vascular smooth muscle cell (SMC) proliferation in vivo, we used an expanded polytetrafluoroethylene (ePTFE)-based local infusion device to deliver an NO donor, proline/NO (PROLI/NO), to the luminal boundary layer of endarterectomized artery and the distal anastomosis of the graft in a canine model. Once delivered to the blood, PROLI/NO releases NO by a mechanism involving pH-dependent decomposition. Six dogs underwent bilateral femoral artery endarterectomies. ePTFE infusion devices, blindly primed with PROLI/NO to one artery or proline to the contralateral vessel, were anastomosed proximal to the injured segments so that each animal served as its own control. PROLI/NO or proline was continuously delivered for 7 days from an osmotic reservoir, through the wall of the graft infusion device. Euthanasia was carried out at 7 days, and the processed specimens were blindly analyzed for SMC proliferation at both graft anastomoses and endarterectomized segments by a bromodeoxyuridine index assay. All dogs survived with no clinical side effects. In comparing the treated and control vessels, NO released from PROLI/NO significantly reduced SMC proliferation by 43% (13.24 +/- 1.24% versus 23.24 +/- 1.01%, P = 0.004) at the distal anastomoses and by 68% (10.58 +/- 1.63% versus 25.17 +/- 3.39%, P = 0.007) at endarterectomized segments. However, there was no significant difference in blood flow measurements between treated and control arteries (56.25 +/- 6.50 ml/min versus 46.50 +/- 3.20 ml/min, P = 0.094). These data demonstrate that local boundary layer infusion of NO released from PROLI/NO significantly reduces SMC proliferation in injured arteries with no effect on regional blood flow. This study suggests a new strategy to inhibit early SMC proliferation in injured arteries and probably to control intimal hyperplastic lesion formation in the manipulated vessels.
为了评估一氧化氮（NO）在体内对血管平滑肌细胞（SMC）增殖的直接作用，我们使用了一种基于膨体聚四氟乙烯（ePTFE）的局部输注装置，在犬模型中向动脉内膜切除术后动脉的管腔边界层以及移植物的远端吻合口输送NO供体脯氨酸/NO（PROLI/NO）。一旦输送到血液中，PROLI/NO通过一种涉及pH依赖性分解的机制释放NO。6只犬接受了双侧股动脉内膜切除术。将预先用PROLI/NO盲法灌注到一条动脉或用脯氨酸灌注到对侧血管的ePTFE输注装置，吻合在损伤段的近端，以便每只动物作为自身对照。PROLI/NO或脯氨酸通过渗透储器从移植物输注装置壁持续输送7天。在第7天实施安乐死，通过溴脱氧尿苷指数测定法对处理后的标本进行盲法分析，以检测移植物吻合口和动脉内膜切除段的SMC增殖情况。所有犬均存活，无临床副作用。在比较处理血管和对照血管时，PROLI/NO释放的NO在远端吻合口使SMC增殖显著降低43%（13.24±1.24%对23.24±1.01%，P = 0.004），在动脉内膜切除段降低68%（10.58±1.63%对25.17±3.39%，P = 0.007）。然而，处理血管和对照动脉之间的血流测量值无显著差异（56.25±6.50 ml/min对46.50±3.20 ml/min，P = 0.094）。这些数据表明，局部边界层输注PROLI/NO释放的NO可显著降低损伤动脉中的SMC增殖，而对局部血流无影响。本研究提示了一种抑制损伤动脉早期SMC增殖并可能控制手术操作血管内膜增生性病变形成的新策略。
