Quyyumi A A, Cannon R O, Panza J A, Diodati J G, Epstein S E
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Circulation. 1992 Dec;86(6):1864-71. doi: 10.1161/01.cir.86.6.1864.
A subgroup of patients with chest pain and angiographically normal epicardial coronary arteries have reduced dilator response to metabolic or pharmacological stimuli, but the mechanisms responsible for this reduced dilator response are unknown. In this study, we have investigated whether microvascular endothelial dysfunction is a cause of the observed reduced vasodilator reserve.
The functional response of the microvasculature was studied with rapid atrial pacing at 150 beats per minute. Fifty-one patients, 20 hypertensive and 31 normotensive, with chest pain and normal epicardial coronary arteries (< 10% stenosis) were studied. Endothelial function was tested with incremental infusions of acetylcholine to achieve estimated intracoronary concentrations ranging from 10(-7) M to 10(-5) M. Endothelium-independent smooth muscle vasomotion was measured using intracoronary sodium nitroprusside. Endothelial dysfunction of epicardial coronary arteries, demonstrated as severe (> 50%) constriction with < 10(-5) M acetylcholine concentration, was evident in five patients (10%). In the remaining 46 patients, coronary blood flow increased with acetylcholine (mean, 78 +/- 43%) and atrial pacing (mean, 51 +/- 37%), and coronary vascular resistance decreased by 35 +/- 16% and 29 +/- 14%, respectively, but the responses were heterogeneous. There was a correlation between the coronary resistance change with acetylcholine and the change with atrial pacing: r = 0.68, p < 0.001 in these 46 patients. Thus, patients with depressed dilation with atrial pacing had reduced endothelium-dependent dilation with acetylcholine, and vice versa. However, the microvascular dilation caused by sodium nitroprusside was not significantly different between patients with and those without reduced dilation with atrial pacing, indicating that the vasodilator defect was not caused by smooth muscle dysfunction. There were no differences in the vasodilator responses with atrial pacing, acetylcholine, or nitroprusside between normotensive and hypertensive patients. Multivariate regression analysis was performed to determine whether age, sex, serum cholesterol level, hypertension, presence of mild epicardial vessel atherosclerosis, resting left ventricular function, change in left ventricular ejection fraction with exercise, vasodilation with acetylcholine, and vasodilation with sodium nitroprusside were independently related to the vasodilator response to atrial pacing. Only the change in coronary vascular resistance with acetylcholine was independently correlated with the change in resistance with atrial pacing: R2 = 0.46, p < 0.0001.
Patients with chest pain, normal epicardial coronary arteries, and reduced vasodilation in response to atrial pacing appear to have associated endothelial dysfunction of the coronary microvasculature. Thus, microvascular endothelial dysfunction may contribute to the reduced vasodilator reserve with atrial pacing and anginal chest pain in these patients.
一组胸痛且心外膜冠状动脉造影正常的患者对代谢或药理刺激的扩张反应降低，但其扩张反应降低的机制尚不清楚。在本研究中，我们调查了微血管内皮功能障碍是否是观察到的血管扩张储备降低的原因。
通过以每分钟150次的频率快速心房起搏研究微血管的功能反应。研究了51例胸痛且心外膜冠状动脉正常（狭窄<10%）的患者，其中20例高血压患者和31例血压正常患者。通过递增输注乙酰胆碱以达到估计的冠状动脉内浓度范围为10⁻⁷M至10⁻⁵M来测试内皮功能。使用冠状动脉内硝普钠测量不依赖内皮的平滑肌血管运动。在5例患者（10%）中，心外膜冠状动脉内皮功能障碍表现为在乙酰胆碱浓度<10⁻⁵M时出现严重（>50%）收缩。在其余46例患者中，冠状动脉血流随乙酰胆碱（平均增加78±43%）和心房起搏（平均增加51±37%）而增加，冠状动脉血管阻力分别降低35±16%和29±14%，但反应存在异质性。在这46例患者中，乙酰胆碱引起的冠状动脉阻力变化与心房起搏引起的变化之间存在相关性：r = 0.68，p < 0.001。因此，心房起搏时扩张功能降低的患者乙酰胆碱介导的内皮依赖性扩张也降低，反之亦然。然而，硝普钠引起的微血管扩张在心房起搏时扩张功能降低和未降低的患者之间无显著差异，表明血管扩张缺陷不是由平滑肌功能障碍引起的。血压正常和高血压患者在心房起搏、乙酰胆碱或硝普钠刺激下的血管扩张反应无差异。进行多变量回归分析以确定年龄、性别、血清胆固醇水平、高血压、轻度心外膜血管动脉粥样硬化的存在、静息左心室功能、运动时左心室射血分数的变化、乙酰胆碱介导的血管扩张以及硝普钠介导的血管扩张是否与心房起搏的血管扩张反应独立相关。只有乙酰胆碱引起的冠状动脉血管阻力变化与心房起搏引起的阻力变化独立相关：R² = 0.46，p < 0.0001。
胸痛、心外膜冠状动脉正常且对心房起搏的血管扩张反应降低的患者似乎存在相关的冠状动脉微血管内皮功能障碍。因此，微血管内皮功能障碍可能导致这些患者心房起搏时血管扩张储备降低和心绞痛性胸痛。
