McLenachan J M, Vita J, Fish D R, Treasure C B, Cox D A, Ganz P, Selwyn A P
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Circulation. 1990 Oct;82(4):1169-73. doi: 10.1161/01.cir.82.4.1169.
Intracoronary acetylcholine produces endothelium-dependent dilation of normal coronary arteries and paradoxical constriction of atherosclerotic vessels. Regional differences in endothelium-dependent vasomotion, however, have not been studied in relation to the nonuniform development of atherosclerosis. We compared the vasomotor response to increasing doses of acetylcholine of angiographically smooth coronary artery segments prone to atherosclerosis (coronary branch points) with segments remote from branch points (straight segments). In patients with entirely smooth coronary arteries and a dilator response to acetylcholine (group 1, n = 7), branch points and straight segments demonstrated equal and significant dose-dependent dilation to acetylcholine (14.7 +/- 8.9% and 12.3 +/- 12.7%, respectively; p identical to NS). In patients with early atherosclerosis as manifest by luminal coronary irregularities, the lowest dose of acetylcholine (10(-8) M) produced constriction at branch points and slight dilation at straight segments (-6.3 +/- 7.4% vs. +2.2 +/- 7.3%, p less than 0.05). At higher doses of acetylcholine, both branch point and straight segments constricted, but constriction remained more pronounced at branch points. Both branch point and straight segments, however, retained the ability to dilate to the non-endothelium-dependent agent, nitroglycerin. In a third group of patients with angiographically entirely smooth coronary arteries but without dilation to acetylcholine, constriction to acetylcholine again occurred first at branch points. Thus, coronary branch points demonstrate increased sensitivity to acetylcholine-induced constriction in patients with angiographic evidence of early coronary atherosclerosis and in middle-aged patients with smooth coronary arteries. These segments, however, retain the ability to dilate to nitroglycerin. Whether this early evidence of defective endothelium-dependent vasodilation predicts the later development of occlusive atherosclerosis is not yet known.
冠状动脉内注射乙酰胆碱可使正常冠状动脉产生内皮依赖性扩张，而使动脉粥样硬化血管出现反常收缩。然而，内皮依赖性血管运动的区域差异尚未与动脉粥样硬化的不均匀发展相关联进行研究。我们比较了易于发生动脉粥样硬化的冠状动脉造影显示光滑的节段（冠状动脉分支点）与远离分支点的节段（直线段）对递增剂量乙酰胆碱的血管运动反应。在冠状动脉完全光滑且对乙酰胆碱有扩张反应的患者中（第1组，n = 7），分支点和直线段对乙酰胆碱均表现出同等且显著的剂量依赖性扩张（分别为14.7±8.9%和12.3±12.7%；p = NS）。在冠状动脉管腔不规则提示早期动脉粥样硬化的患者中，最低剂量的乙酰胆碱（10⁻⁸ M）在分支点引起收缩，在直线段引起轻微扩张（-6.3±7.4%对+2.2±7.3%，p < 0.05）。在较高剂量的乙酰胆碱作用下，分支点和直线段均发生收缩，但分支点的收缩更为明显。然而，分支点和直线段对非内皮依赖性药物硝酸甘油仍保留扩张能力。在第三组冠状动脉造影显示完全光滑但对乙酰胆碱无扩张反应的患者中，对乙酰胆碱的收缩同样首先发生在分支点。因此，在有早期冠状动脉粥样硬化血管造影证据的患者以及冠状动脉光滑的中年患者中，冠状动脉分支点对乙酰胆碱诱导的收缩敏感性增加。然而，这些节段对硝酸甘油仍保留扩张能力。内皮依赖性血管舒张功能缺陷的这一早期证据是否预示着闭塞性动脉粥样硬化的后期发展尚不清楚。
