冠状动脉疾病患者同一冠状动脉相邻节段对冠状动脉内乙酰胆碱的收缩和舒张反应。重新审视内皮功能。

Constrictor and dilator responses to intracoronary acetylcholine in adjacent segments of the same coronary artery in patients with coronary artery disease. Endothelial function revisited.

作者信息

el-Tamimi H, Mansour M, Wargovich T J, Hill J A, Kerensky R A, Conti C R, Pepine C J

机构信息

Division of Cardiology, University of Florida, Gainesville 32610-0277.

出版信息

Circulation. 1994 Jan;89(1):45-51. doi: 10.1161/01.cir.89.1.45.

DOI:10.1161/01.cir.89.1.45

PMID:8281679

Abstract

BACKGROUND

In patients with angiographically detectable atherosclerosis or in those with risk factors for coronary artery disease, intracoronary acetylcholine causes coronary constriction instead of endothelium-derived relaxing factor-mediated dilation. Therefore, it has been hypothesized that diffuse endothelial dysfunction precedes development of coronary atherosclerosis. We tested this hypothesis in a systematic investigation of the effects of ascending doses of acetylcholine on the diameters of nonstenotic segments of the left coronary artery in patients with advanced atherosclerosis and coronary risk factors.

METHODS AND RESULTS

Effects of intracoronary infusion of acetylcholine (10(-6) to 10(-4) mol/L) on diameters of proximal, middle, and distal nonstenotic segments of the left coronary artery were studied in 28 consecutive patients with chronic stable angina, positive exercise tests, and angiographic evidence of obstructive atherosclerosis (> or = 50% reduction in lumen diameter in at least one vessel). Two patterns of response to the maximal acetylcholine dose (10(-4) mol/L) were observed. In 21 patients (group 1), only constriction was observed in all left anterior descending and circumflex artery segments studied (16 +/- 3%, 19 +/- 4%, and 23 +/- 4%, respectively; P < .01 compared with control). In 7 other patients (group 2), both constriction and dilation were observed in adjacent segments of the same vessel; maximal acetylcholine dose caused constriction in 14 left anterior descending artery segments from a control diameter of 1.94 +/- 0.19 to 1.33 +/- 0.26 mm (37% reduction, P < .01) and dilation in 16 other segments from 1.63 +/- 0.22 to 1.93 +/- 0.21 mm (25% increase, P < .01). In the circumflex artery, this dose caused constriction in 16 segments from a control diameter of 1.88 +/- 0.14 to 1.33 +/- 0.17 mm (31% reduction, P < .01) and dilation in 12 segments from 1.37 +/- 0.12 to 1.71 +/- 0.09 mm (34% increase, P < .01).

CONCLUSIONS

In 25% of patients studied with advanced angiographic coronary atherosclerosis and coronary risk factors, coronary segments with acetylcholine-inducible dilatation are present. In these patients, the endothelium is not diffusely dysfunctional as currently believed but rather shows marked segmental heterogeneity in the response to acetylcholine reflecting degrees of endothelial dysfunction.

摘要

背景

在血管造影可检测到动脉粥样硬化的患者或有冠状动脉疾病危险因素的患者中，冠状动脉内注射乙酰胆碱会导致冠状动脉收缩，而非内皮源性舒张因子介导的扩张。因此，有人提出弥漫性内皮功能障碍先于冠状动脉粥样硬化的发生。我们通过系统研究递增剂量的乙酰胆碱对患有晚期动脉粥样硬化和冠状动脉危险因素患者左冠状动脉非狭窄节段直径的影响来验证这一假设。

方法与结果

对28例连续的慢性稳定型心绞痛、运动试验阳性且有阻塞性动脉粥样硬化血管造影证据（至少一支血管管腔直径减少≥50%）的患者，研究冠状动脉内注射乙酰胆碱（10⁻⁶至10⁻⁴mol/L）对左冠状动脉近端、中段和远端非狭窄节段直径的影响。观察到对最大乙酰胆碱剂量（10⁻⁴mol/L）有两种反应模式。在21例患者（第1组）中，在所有研究的左前降支和回旋动脉节段均仅观察到收缩（分别为16±3%、19±4%和23±4%；与对照组相比，P<.01）。在其他7例患者（第2组）中，在同一血管的相邻节段观察到收缩和扩张；最大乙酰胆碱剂量导致14个左前降支动脉节段从对照直径1.94±0.19mm收缩至1.33±0.26mm（减少37%，P<.01），而其他16个节段从1.63±0.22mm扩张至1.93±0.21mm（增加25%，P<.01）。在回旋动脉中，该剂量导致16个节段从对照直径1.88±0.14mm收缩至1.33±0.17mm（减少31%，P<.01），12个节段从1.37±0.12mm扩张至1.71±0.09mm（增加34%，P<.01）。