Heckenkamp J, Mellander S, Fogelstrand P, Breuer S, Brunkwall J, Mattsson E
Division of Vascular Surgery, Department of Vascular and Visceral Surgery, University of Cologne, Cologne, Germany.
Eur J Vasc Endovasc Surg. 2007 Sep;34(3):333-9. doi: 10.1016/j.ejvs.2007.04.002. Epub 2007 May 21.
Bypass surgery has a failing frequency of 30% during the first year, mainly due to intimal hyperplasia (IH). This negative effect is most pronounced in artificial grafts. Photodynamic therapy (PDT) is a technique in which light activates photosensitizer dyes to produce free-radicals resulting in an eradication of cells in the vascular wall. The aim of this study was to determine the effectiveness of PDT to reduce IH in a preclinical porcine PTFE bypass model.
Ten pigs were used. After a pilot PDT dosimetry study (n=3) PTFE grafts were bilaterally placed into the circulation as bypasses from the common to the external iliac arteries (n=7). The right sides served as controls (C). Before implantation of the left grafts, the arterial connecting sites of the left distal anastomoses were PDT-treated. The arteries were pressurized at 180 mmHg for 5 minutes with the photosensitizer Methylene Blue (330 microg/ml), and thereafter endoluminally irradiated with laser light (lambda = 660 nm, 100 mW/cm(2), 150 J/cm(2)). After 4 weeks the specimens were retrieved and formalin fixed. Cross sections through the midportions of the distal anastomoses and the grafts were used for histology, immunohistochemistry to identify inflammatory cells and morphometric evaluation (n=7).
No systemic side effects and no graft occlusions were noted. PDT-treated anastomoses showed reduced IH in the mid-portions of the anastomoses (Area of IH: microm(2)/microm graft: C: 6970+/-1536, PDT: 2734+/-2560; P<0.005) as well as in the grafts (C: 5391+/-4031, PDT: 777+/-1331; P<0.02). The number of inflammatory cells per microscopic field was increased after PDT (C: 24+/-16, PDT: 37+/-15; P<0.009).
Adjuvant PDT, performed in an endovascular fashion, was a safe method to reduce prosthetic graftstenosis in a preclinical setting. This study underscores the clinical potential of PDT to inhibit the development of clinical bypass graftstenosis.
搭桥手术在第一年的失败率为30%，主要原因是内膜增生（IH）。这种负面影响在人工移植物中最为明显。光动力疗法（PDT）是一种技术，其中光激活光敏染料以产生自由基，从而消除血管壁中的细胞。本研究的目的是确定光动力疗法在临床前猪PTFE搭桥模型中减少内膜增生的有效性。
使用10头猪。在一项光动力疗法剂量测定预试验研究（n = 3）后，将PTFE移植物双侧植入循环系统，作为从总髂动脉到外髂动脉的搭桥（n = 7）。右侧作为对照（C）。在植入左侧移植物之前，对左侧远端吻合口的动脉连接部位进行光动力疗法治疗。用光敏剂亚甲蓝（330微克/毫升）将动脉在180毫米汞柱压力下加压5分钟，然后用激光（波长=660纳米，100毫瓦/平方厘米，150焦耳/平方厘米）进行腔内照射。4周后取出标本并用福尔马林固定。通过远端吻合口和移植物中部的横截面用于组织学、免疫组织化学以识别炎症细胞和形态计量学评估（n = 7）。
未观察到全身副作用和移植物闭塞。光动力疗法治疗的吻合口在吻合口中部显示内膜增生减少（内膜增生面积：平方微米/微米移植物：C组：6970±1536，光动力疗法组：2734±2560；P < 0.005），在移植物中也是如此（C组：5391±4031，光动力疗法组：777±1331；P < 0.02）。光动力疗法后每个显微镜视野中的炎症细胞数量增加（C组：24±16，光动力疗法组：37±15；P < 0.009）。
以血管内方式进行的辅助光动力疗法是在临床前环境中减少人工移植物狭窄的安全方法。本研究强调了光动力疗法抑制临床搭桥移植物狭窄发展的临床潜力。
