次高温热球囊及冷冻球囊血管成形术的初步研究

Percutaneous transluminal angioplasty by using sub-hyperthermia balloon or freezing-balloon: a preliminary study

目的探讨用次高温热球囊及冷冻球囊处理动脉狭窄模型的可行性及最佳效果参数。方法取动脉粥样硬化性狭窄动物模型,采用热球囊及冷冻球囊扩张髂内动脉粥样硬化狭窄段。将符合研究条件的实验对象(6头长白猪)分为A组(热球囊,42～50℃,扩张10 min)、B组(热球囊,42～50℃,扩张20 min)和C组(冷冻球囊,-10℃,扩张2 min),每组2头。DSA下导入球囊至血管狭窄段,在X线透视下,向球囊注入载热液体或氧化亚氮介质扩张球囊,同时用高灵敏温度测量仪实时测量球囊局部靶血管壁所承受的热、冷负荷。血管成形术后4周行病理学检查,动物处死前均行血管造影。观察局部血管对次高温、浅低温的反应及演变过程。结果 A、B、C组的血管横断面积分别为(263 653.76±251 422.46)μm2、(348 123.68±199 871.47)μm2和(260 960.68±141 244.12)μm2,B组大于A组和C组(P=0.003 7);每高倍镜视野内膜平滑肌细胞数目及管腔狭窄指数分别为(289±34)个和0.49±0.18、(330±105)个和0.78±0.17、(232±66)个和0.57±0.19,B组亦高于A组和C组(P=0.000 1);中膜面积及内膜面积分别为(545 198.09±64 574.07)μm2和(178 497.16±83 903.75)μm2、(543 880.64±66 129.98)μm2和(84 640.09±55 330.06)μm2、(640 743.85±262 858.74)μm2和(263 897.40±268 037.66)μm2,C组大于A组和B组(P=0.000 1);内膜/中膜面积比(代表内膜增生程度)及内膜增生指数分别为0.34±0.19和0.25±0.11、0.16±0.10和0.13±0.07、0.42±0.50和0.24±0.19,B组低于A组和C组(P=0.000 1)。结论局部导入"次高温"或"浅低温"均可抑制平滑肌细胞增殖、移行和分泌基质,从而可能会降低血管成形术后远期再狭窄率,最佳效果参数为次高温42～50℃,扩张时间20 min。

Objective To investigate the feasibility of percutaneous transluminal angioplasty by using sub-hyperthermia balloon or freezing-balloon in experimental animals, and to discuss the optimal thermal parameters. Methods Six pigs with atherosclerotic stenosis were used in this study. The pigs were randomly divided into three groups： group A, B and C. The percutaneous transluminal angioplasty by using sub hyperthermia balloon or freezing-balloon was employed to treat the stenotic arterial segment. Sub hyperthermia balloon （42℃-50℃ ） dilatation （10 min） was used in the pigs of group A, while sub hyperthermia balloon （42℃-50℃） dilatation （20 min） was adopted in the pigs of group B. For the pigs of group C, freezing- balloon（-10℃） dilatation（2 min） was conducted. The thermal energy was introduced into the target vessels by using balloon that was filled with liquid medium of certain temperature and nitrous oxide gas under fluoroscopic guidance and the temperature upon the target vessel’s wall was monitored by high sensitive intra-cavity temperature measurement system. Angiography was carried out just before the animal was sacrificed. The specimens were collected and sent for pathologic examination to observe the vascular reaction to sub -hyperthermia and hypothermia. Results The arterial transverse section areas in group A, B and c were （263 653.76 ± 251 422.46） um 2 , （348 123.68 ± 199 871.47） um 2 and （260 960.68 ± 141 244.12） um 2 , respectively. The arterial transverse section area of group B was significantly larger than that of group A as well as of group C （P = 0.003 7）. The intimal smooth muscle cell numbers microscopically determined under high magnification in group A, B and C were （289 ± 34）, （330 ± 105） and （232 ± 66） respectively, and the luminal stenosis indexes in group A, B and C were （0.49 ± 0.18）, （0.78 ± 0.17） and （0.57 ± 0.19） respectively. Both the intimal smooth muscle cell numbers and the luminal stenosis index of group B were higher than that of group A as well as of group C（P = 0.000 1）. The arterial medium areas of group A, B and C were （545 198.09 ± 64 574.07） um 2 , （543 880.64 ± 66 129.98） um 2 and （640 743.85 ± 262 858.74） um 2 respectively , and the neointimal areas of group A , B and C were （178 497.16 ± 83 903.75） um 2 , （84 640.09 ± 55 330.06） um 2 and （263 897.40 ± 268 037.66） um 2 respectively. The sizes of the two areas of group C were larger than those of group A and group B （P = 0.000 1）. The intima- to- medium area ratio, as an indication of the degree of intimal proliferation, of group A, B and C was （0.34 ± 0.19）, （0.16 ± 0.10） and （0.42 ± 0.50） respectively, while the intima hyperplasia index of group A, B and C was （0.25 ± 0.11）, （0.13 ± 0.07） and （0.24 ± 0.19） respectively. The above values of group B were significantly lower than those of group A and group C （P = 0.000 1）. Conclusion The local application of sub-hyperthermia and the hypothermia can effectively inhibit the proliferation, migration and secretion of the vascular smooth muscle cell, therefore the long-term re-stenosis rate after angioplasty can be possibly reduced. The optimal temperature is 40℃ to 45℃, and the recommended dilatation time is 20 min.