Zeiher A M, Krause T, Schächinger V, Minners J, Moser E
Department of Internal Medicine, University of Freiburg, Germany.
Circulation. 1995 May 1;91(9):2345-52. doi: 10.1161/01.cir.91.9.2345.
The release of endothelium-derived relaxing factors has been shown experimentally to be of pivotal importance for the maintenance of coronary blood flow during increased demand. In humans with coronary atherosclerosis, endothelial vasodilator dysfunction is not confined only to epicardial conductance vessels but may also extend into the coronary microcirculation. We therefore tested the hypothesis that endothelial vasodilator dysfunction of the coronary resistance vasculature is associated with myocardial ischemia during exercise in patients without hemodynamically significant epicardial artery stenoses.
Coronary vasodilator function was assessed by subselective infusion of the endothelium-dependent dilator acetylcholine (0.036 to 3.6 micrograms/mL) and the endothelium-independent dilator papaverine (7 mg). Coronary blood flow responses were evaluated by intracoronary Doppler flow velocity recordings and quantitative angiography. Exercise-induced myocardial perfusion was determined by 201Tl single photon emission computed tomographic imaging. Thirteen patients had exercise-induced myocardial perfusion defects suggestive of myocardial ischemia, whereas 14 patients had normal thallium imaging during exercise. In patients with exercise-induced thallium perfusion defects, coronary blood flow responses to acetylcholine were significantly (P < .005) blunted compared with patients with normal thallium imaging during exercise. In contrast, coronary blood flow reserve to the endothelium-independent smooth muscle relaxant papaverine was similar in the two groups. Patients with exercise-induced thallium perfusion defects exhibited a significantly (P < .005) reduced (23.9 +/- 9.0% [mean +/- SD]) endothelium-mediated coronary vasodilator capacity compared with patients with normal thallium testing (56.2 +/- 27.8%). Epicardial artery vasoreactivity to acetylcholine did not differ between the two groups.
Impaired endothelium-dependent vasodilation of the coronary microcirculation is associated with exercise-induced myocardial ischemia in patients without hemodynamically significant epicardial artery lesions. Endothelial vasodilator dysfunction extending into the coronary microcirculation may thus contribute to the ischemic manifestations of coronary artery disease during times of increased myocardial demand.
实验表明，内皮源性舒张因子的释放对于需求增加时冠状动脉血流的维持至关重要。在患有冠状动脉粥样硬化的人类中，内皮血管舒张功能障碍不仅局限于心外膜传导血管，还可能延伸至冠状动脉微循环。因此，我们检验了以下假设：在没有血流动力学显著意义的心外膜动脉狭窄的患者中，冠状动脉阻力血管的内皮血管舒张功能障碍与运动期间的心肌缺血相关。
通过亚选择性输注内皮依赖性舒张剂乙酰胆碱（0.036至3.6微克/毫升）和内皮非依赖性舒张剂罂粟碱（7毫克）来评估冠状动脉舒张功能。通过冠状动脉内多普勒流速记录和定量血管造影来评估冠状动脉血流反应。通过201Tl单光子发射计算机断层扫描成像来确定运动诱发的心肌灌注。13例患者有运动诱发的心肌灌注缺损，提示心肌缺血，而14例患者在运动期间铊显像正常。与运动期间铊显像正常的患者相比，有运动诱发铊灌注缺损的患者对乙酰胆碱的冠状动脉血流反应明显（P <.005）减弱。相比之下，两组对内皮非依赖性平滑肌舒张剂罂粟碱的冠状动脉血流储备相似。与铊试验正常的患者相比，有运动诱发铊灌注缺损的患者内皮介导的冠状动脉舒张能力明显（P <.005）降低（23.9±9.0%[平均值±标准差]），而正常铊试验患者为（56.2±27.8%）。两组心外膜动脉对乙酰胆碱的血管反应性无差异。
在没有血流动力学显著意义的心外膜动脉病变的患者中，冠状动脉微循环的内皮依赖性舒张受损与运动诱发的心肌缺血相关。因此，延伸至冠状动脉微循环的内皮血管舒张功能障碍可能在心肌需求增加时导致冠状动脉疾病的缺血表现。
