Drexler H, Zeiher A M
Medizinische Klinik III, University of Freiburg, FRG.
Hypertension. 1991 Oct;18(4 Suppl):II90-9. doi: 10.1161/01.hyp.18.4_suppl.ii90.
To examine whether and to what extent hypercholesterolemia may affect the vasoactive role of the endothelium before the onset of angiographically visible atherosclerosis in the coronary circulation, we studied normal subjects (group 1, n = 11), individuals with elevated low density lipoprotein plasma values but angiographically smooth coronary arteries (group 2, n = 8), and patients with hypercholesterolemia and minimal disease of the vessel under study (group 3, n = 8). Coronary vasomotor function was evaluated by three interventions: subselective intracoronary infusion of acetylcholine (0.036, 0.36, and 3.6 micrograms/min) with a 3F Doppler catheter in the left anterior descending artery, 0.3 mg intracoronary nitroglycerin ("endothelium-independent"), and increase in blood flow (assessment of flow-dependent, endothelium-mediated coronary dilation). In group 1, all interventions caused coronary dilation of the left anterior descending artery as assessed by automatic quantification of digitized cineframes. However, in group 2, acetylcholine elicited substantial coronary vasoconstriction, and the vasodilator response to nitroglycerin and to increases in flow (flow-dependent dilation) was preserved. In group 3, the acetylcholine-induced coronary vasoconstriction was even more pronounced, and the flow-dependent dilation was impaired (+5.1 +/- 1% versus +10.5 +/- 1.1% [group 1], p less than 0.05). The coronary flow reserve (derived from Doppler flow velocity measurements) in response to papaverine was not significantly different in normal and hypercholesterolemic individuals (groups 2 and 3). However, the increase in coronary flow exerted by acetylcholine was substantially depressed in patients with hypercholesterolemia (groups 2 and 3) as compared with normal individuals (+48 +/- 8.3% and +49 +/- 25% versus +220 +/- 28.5%, respectively, p less than 0.01). Thus, hypercholesterolemia elicits endothelial dysfunction in coronary conduit and resistance vessels in humans that precedes angiographically visible atherosclerotic lesions in large coronary arteries. Conceivably, these vascular alterations contribute to increased coronary vasomotor tone within the coronary circulation and may predispose these patients to myocardial ischemia.
为了研究在冠状动脉循环中血管造影可见的动脉粥样硬化出现之前，高胆固醇血症是否以及在何种程度上会影响内皮的血管活性作用，我们研究了正常受试者（第1组，n = 11）、低密度脂蛋白血浆值升高但冠状动脉造影显示血管光滑的个体（第2组，n = 8）以及患有高胆固醇血症且所研究血管病变轻微的患者（第3组，n = 8）。通过三种干预措施评估冠状动脉血管运动功能：在左前降支动脉中使用3F多普勒导管进行选择性冠状动脉内注入乙酰胆碱（0.036、0.36和3.6微克/分钟）、冠状动脉内注入0.3毫克硝酸甘油（“不依赖内皮”）以及增加血流量（评估血流依赖性、内皮介导的冠状动脉扩张）。在第1组中，通过对数字化电影帧的自动定量评估，所有干预措施均导致左前降支动脉冠状动脉扩张。然而，在第2组中，乙酰胆碱引起显著的冠状动脉收缩，而对硝酸甘油和血流量增加（血流依赖性扩张）的血管舒张反应得以保留。在第3组中，乙酰胆碱诱导的冠状动脉收缩更为明显，且血流依赖性扩张受损（+5.1±1% 对比 +10.5±1.1% [第1组]，p < 0.05）。正常人和高胆固醇血症个体（第2组和第3组）对罂粟碱反应的冠状动脉血流储备（源自多普勒流速测量）无显著差异。然而，与正常个体相比，高胆固醇血症患者（第2组和第3组）中乙酰胆碱引起的冠状动脉血流增加显著降低（分别为+48±8.3% 和 +49±25% 对比 +220±28.5%，p < 0.01）。因此，高胆固醇血症在人类冠状动脉导管和阻力血管中引发内皮功能障碍，这发生在大冠状动脉血管造影可见的动脉粥样硬化病变之前。可以想象，这些血管改变导致冠状动脉循环中冠状动脉血管运动张力增加，并可能使这些患者易患心肌缺血。
