Gabeler E E E, van Hillegersberg R, Statius van Eps R G, Sluiter W, Mulder P, van Urk H
Department of Surgery, University Hospital Rotterdam-Dijkzigt, Erasmus MC, Room H928, Dr Molewaterplein 40, 3015 GE Rotterdam, The Netherlands.
Eur J Vasc Endovasc Surg. 2002 Oct;24(4):322-31. doi: 10.1053/ejvs.2002.1723.
intimal hyperplasia (IH) and constrictive remodelling are important causes of restenosis following endovascular interventions, such as percutaneous transluminal angioplasty. Photodynamic therapy (PDT) with 5-aminolaevulinic (ALA) may prevent restenosis by cellular depletion and the elimination of cholinergic innervation.
STUDY DESIGN/MATERIALS AND METHODS: rats (n=90) were subdivided into 4 main groups. In the experimental group (n=36: 3 replications x 4 doses x 3 examination time-points), ALA was administered (200mg/kg i.v.) 2-3h before balloon injury (BI) of the common iliac artery followed by endovascular illumination with 633nm at either 12.5, 25, 50 or 100J/cm diffuser length (dl BI+PDT group). As control groups served the BI+Light only (LO) group (n=36) that received no ALA, the BI only group (n=9) (BI), and a group (n=9) that received a Sham procedure (Sham group).
planimetric analysis showed IH of 0.28+/-0.12mm(2) (BI), 0.27+/-0.12mm(2) (BI+LO at 100J/cmdl) in contrast to 0.02+/-0.02mm(2) after BI+PDT at 100J/cmdl at 16 weeks (p<0.05). In the BI+PDT groups, a light-dose increase of a factor 2 led to an IH decrease of 17% (p<0.05). In the BI and BI+LO groups constrictive remodelling was found, in contrast to BI+PDT treated groups at 16 weeks. The staining of cholinergic innervation of the tunic media of the blood vessel wall in BI+PDT showed no damage at the highest fluence.
endovascular ALA-PDT prevents IH and constrictive remodelling after BI without damage of cholinergic innervation of the tunica media. The effective light fluence rate in the rat is 50-100J/cmdl.
内膜增生(IH)和血管收缩性重塑是血管腔内介入治疗(如经皮腔内血管成形术)后再狭窄的重要原因。5-氨基酮戊酸(ALA)光动力疗法(PDT)可能通过细胞耗竭和消除胆碱能神经支配来预防再狭窄。
研究设计/材料与方法:将90只大鼠分为4个主要组。在实验组(n = 36:3次重复×4个剂量×3个检查时间点)中,在对髂总动脉进行球囊损伤(BI)前2 - 3小时静脉注射ALA(200mg/kg),随后以12.5、25、50或100J/cm扩散器长度(dl BI + PDT组)用633nm进行血管腔内照射。作为对照组的是未接受ALA的BI + 仅光照(LO)组(n = 36)、仅BI组(n = 9)(BI)以及接受假手术的组(假手术组,n = 9)。
平面测量分析显示,16周时,BI组内膜增生为0.28±0.1(2)mm,BI + LO组(100J/cm dl)为0.27±0.12mm,而BI + PDT组(100J/cm dl)为0.02±0.02mm(p < 0.05)。在BI + PDT组中,光剂量增加2倍导致内膜增生减少17%(p < 0.05)。在BI组和BI + LO组中发现了血管收缩性重塑,而16周时BI + PDT治疗组未出现。BI + PDT组中血管壁中膜胆碱能神经支配的染色在最高光通量下未显示损伤。
血管腔内ALA - PDT可预防BI后的内膜增生和血管收缩性重塑,且不会损伤中膜的胆碱能神经支配。大鼠的有效光通量率为50 - 100J/cm dl。