Newman C M, Maseri A, Hackett D R, el-Tamimi H M, Davies G J
Division of Cardiovascular Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Am J Cardiol. 1990 Nov 1;66(15):1070-6. doi: 10.1016/0002-9149(90)90507-w.
Acetylcholine-induced constriction of human coronary arteries in vivo is commonly attributed to endothelial dysfunction. To examine the effects of 2 other important determinants of vascular responses--namely, agonist concentration and the segment of circulation under study--the diameters of proximal, middle and distal segments of the left anterior descending artery (LAD) and coronary sinus oxygen saturation were measured in 10 patients with angiographically normal coronary arteries (group 1) and in 7 patients with coronary atherosclerosis (group 2) after intracoronary acetylcholine was infused at concentrations from 10(-7)M to between 10(-4)M and 10(-2)M. In group 1, acetylcholine caused minor (less than or equal to 6%) but progressive dilatation of the LAD up to 10(-4)M, but constriction, particularly of the distal segments and tertiary branches, occurred at higher concentrations. Over the same concentration range, coronary sinus oxygen saturation rose progressively from a basal level of 36 +/- 3% to a maximum of 72 +/- 3% in the absence of changes in heart rate and blood pressure, suggesting marked progressive dilatation of resistance vessels. Concentrations greater than or equal to 10(-3)M caused intense constriction of distal epicardial vessels and, in some cases, anginal pain and objective signs of ischemia. Conversely, in group 2, acetylcholine (infused only up to 10(-4)M for ethical reasons) failed to cause significant changes in LAD diameter. These data suggest that the local acetylcholine concentration and coronary vascular segment under study may determine the observed response to at least an equivalent extent as does the presence or absence of coronary atherosclerosis, raising the question of whether a constrictor response to intracoronary acetylcholine reliably indicates the presence of coronary atherosclerosis.
体内乙酰胆碱引起的人冠状动脉收缩通常归因于内皮功能障碍。为了研究血管反应的另外两个重要决定因素——即激动剂浓度和所研究的循环节段——在10例冠状动脉造影正常的患者（第1组）和7例冠状动脉粥样硬化患者（第2组）中，在冠状动脉内注入浓度从10⁻⁷M至10⁻⁴M与10⁻²M之间的乙酰胆碱后，测量左前降支（LAD）近端、中段和远端节段的直径以及冠状窦血氧饱和度。在第1组中，乙酰胆碱在浓度达到10⁻⁴M时引起LAD轻微（≤6%）但逐渐的扩张，但在更高浓度时会发生收缩，尤其是远端节段和三级分支。在相同浓度范围内，冠状窦血氧饱和度在心率和血压无变化的情况下从基础水平36±3%逐渐上升至最高72±3%，提示阻力血管明显逐渐扩张。浓度≥10⁻³M会导致远端心外膜血管强烈收缩，在某些情况下会引起心绞痛和缺血的客观体征。相反，在第2组中，出于伦理原因仅注入至10⁻⁴M的乙酰胆碱未能引起LAD直径的显著变化。这些数据表明，所研究的局部乙酰胆碱浓度和冠状动脉血管节段可能至少在同等程度上决定观察到的反应，如同冠状动脉粥样硬化的有无一样，这就提出了一个问题，即对冠状动脉内乙酰胆碱的收缩反应是否能可靠地表明冠状动脉粥样硬化的存在。
