Mechanisms of Restenosis Following Coronary Angioplasty and its Prevention

尽管经皮冠状动脉腔内成形术(PTCA)已广泛应用于冠心病患者，但术后再狭窄发生率高达近50%，仍是最严重的并发症之一。本研究旨在探讨球囊导管致小型猪血管内膜加速增殖的相关因素、机制及预防措施。给予添加2%胆固醇和氯酸钠的半合成饮食诱导高胆固醇血症，增强动脉粥样硬化进程。我们发现了以下几个有趣的现象：(1)自发性冠状动脉狭窄在球囊内膜损伤后出现，5min后逐渐达到最大水平(狭窄60%)。静脉注射肝素3000单位或酮色林可部分阻止这种增强的收缩。对5-羟色胺的夸大反应持续2周，但不是4周。(2)X射线照射本身可增强对5-羟色胺的反应。照射后4周可见内膜增厚。(3)剥脱加X射线照射可增强血管对5-羟色胺的收缩反应，增加血管内膜厚度。附加的PTCA可减弱5-羟色胺引起的狭窄程度，而这种方法可增加血管内膜增厚的速度。因此，本动物模型可能为阐明血管成形术相关再狭窄的发生机制提供依据。这些基础研究将探索防止血管内膜加速增厚的治疗方法。

Although the percutaneous transluminal coronary angioplasty (PTCA) has commonly been applied to patients with coronary artery disease, high incidence of restenosis close to 50%, following the procedure remains one of the most serious complications. The goal of the present study was to elucidate the factors, mechanisms and prevention related to the accelerated proliferation of the intima, injured by a balloon catheter in Gottingen miniature pigs. Semisynthetic diet added cholesterol 2% and sodium chlorate was given to induce hypercholesterolemia and to augment the atherosclerotic process. We disclosed several interesting phenomena as follows ; (1) Spontaneous coronary constriction was noted after the balloon-induced intimal injury and reached gradually by 5 minutes the maximum level (60% narrowing). The augmented constriction was partly prevented by intravenous administration of heparin 3000 units or ketanserin. Exaggerated response to serotonin remained for 2 but not 4 weeks. (2) X-ray irradiation per se enhanced responses to serotonin. Intimal thickening was noted 4 weeks after the irradiation. (3) Denudation plus X-ray irradiation augmented the constrictive responses to serotonin as well as the thickening of the intima. Additional PTCA attenuated the extent of serotonin-induced constriction while this procedure augmented the speed of intimal thickening. Accordingly, the present animal model may provide keys to elucidate the mechanisms of ensuing restenosis related to the angioplasty. Remedies to prevent accelerated intimal thickening will be explored by these basic studies.