Mechanisms of Restenosis Following Coronary Angioplasty and its Prevention

冠状动脉成形术后再狭窄的机制及其预防

• 批准号: 02454259
• 负责人: TOMOIKE Hitonobu
• 金额: $ 4.35万
• 依托单位: Yamagata University School of Medicine (1991)Kyushu University (1990)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454259/
• 关键词: atherosclerosis; coronary artery stenosis; PTCA; coronary artery spasm; restenosis; platelet; serotonin; X-ray irradiation; 内膜肥厚; PTcA; 内皮細胞依存性血管弛緩反応; 心筋虚血; 冠動脈硬化; 冠血行再建術; 血管内皮細胞; ミニ豚; 冠動脈造影法

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.

尽管经皮腔内冠状动脉成形术（PTCA）已广泛应用于冠状动脉疾病患者，但该手术后再狭窄的发生率高达50%，仍然是最严重的并发症之一。本研究的目的是阐明哥廷根微型猪气囊导管损伤内膜加速增殖的相关因素、机制和预防措施。采用添加2%胆固醇和氯酸钠的半合成日粮诱导高胆固醇血症，增强动脉粥样硬化过程。我们揭示了以下几个有趣的现象：(1)球囊引起的冠状动脉内膜损伤后出现自发性冠状动脉收缩，并在5分钟后逐渐达到最大水平（狭窄60%）。静脉滴注肝素3000单位或酮色林可部分预防收缩增强。对血清素的过度反应持续了2周而不是4周。(2) x射线照射本身增强了对血清素的反应。照射后4周内膜增厚。(3)剥脱加上x射线照射增强了对血清素的收缩反应以及内膜的增厚。额外的PTCA减轻了血清素诱导的收缩程度，而这一过程增加了内膜增厚的速度。因此，本动物模型可能为阐明血管成形术后继发再狭窄的机制提供关键。这些基础研究将探讨预防加速内膜增厚的方法。

项目成果

Sato S, Tomoike H, Mitsuoka W, Egashia S, Tagawa H, Kuga T, Nakamura M: "Smooth muscles from the spastic coronary artery segments shows hypercontractility to histamine." Am J Physiol. 259(1). H9-H13 (1990)

Sato S、Tomoike H、Mitsuoka W、Egashia S、Takawa H、Kuga T、Nakamura M：“痉挛的冠状动脉段的平滑肌表现出对组胺的过度收缩。”

Tagawa H, Tomoike H, Nakamura M: "Putative mechanisms of the impairment of endo-thelium-dependent relaxation of the aorta with atheromatous plaque in hereditary hyperlipidemic rabbits." Circ Res. 68(2). 330-337 (1991)

Takawa H、Tomoike H、Nakamura M：“遗传性高脂血症兔中动脉粥样硬化斑块对主动脉内皮依赖性舒张造成损害的推定机制。”

Tomoike H, Egashira K, Yamamoto Y, Shimokawa H, Hayashi Y, Yamada A, Nanasawa K, Mitsuoka W, Egashira S, Kuga T, Tagawa H, Nakamura M: "Cascade of pathophysiological events leading to spasm of coronary arteries." Regulation of Coronary Blood Flow. Springe

Tomoike H, Egashira K, Yamamoto Y, Shimokawa H, Hayashi Y, Yamada A, Nanasawa K, Mitsuoka W, Egashira S, Kuga T, Takawa H, Nakamura M：“导致冠状动脉痉挛的病理生理事件级联。”

Tomoike H: "Coronary spasm and integrity of endothelial function" Jpn Circ J. 56. 175-177 (1992)

Tomoike H：“冠状动脉痉挛和内皮功能的完整性”Jpn Circ J. 56. 175-177 (1992)

Yamaki M,et al: "Relation between recovery sequence estimated from body surface potentials and T wave shape in patients with negative T waves and normal subjects." Circulation. 85. (1992)

Yamaki M 等人：“从体表电位估计的恢复序列与负 T 波患者和正常受试者的 T 波形状之间的关系。”