Pathophysiological evaluation and treatment of coronary microvessel disorders in humans

我们研究了冠状动脉微血管疾病（CMD）的1）如何检测缺血证据，2）冠状动脉血流动力学特征，3）腺苷动力学，4）内皮依赖性舒张（EDR），5）脂质代谢，和6）针对缺血诱导机制的药物治疗。结果表明：（1）快速心房起搏时冠状静脉血氧饱和度持续下降（>5%）是CMD患者心肌缺血的早期征象。2)CMD患者左心室心尖区的室壁运动功能减退，并在潘生丁诱导的缺血期间显示左心室心肌超声白蛋白斑片状增强，提示冠状动脉盗血现象。3)CMD和对照组受试者在缺血期间的动脉和静脉腺苷浓度无差异。4)CMD组冠状动脉微血管EDR明显低于对照组，而冠状动脉导管EDR与对照组相似。5)CMD组和对照组的T-chol、HDL-chol和LDL-chol无差异。但CMD患者血清氧化型LDL水平明显高于对照组。6)氨茶碱和ACE抑制剂可减轻CMD患者运动时心电图ST段下移。特别是，长期服用ACE抑制剂（3个月）似乎不仅可以减少CMD患者的ECG ST-dep，还可以减少CMD患者的主观主诉。这些结果提示，氧化LDL可能通过冠状动脉盗血现象特异性损伤冠状动脉前血管内皮，导致微血管缺血。因此，我们认为ACE抑制剂对CMD患者是有效的。

We investigated coronary microvessel disorder (CMD) in terms of 1) how to detect ischemic evidence, 2) coronary hemodynamic characteristics, 3) adenosine dynamics, 4) endothelium-dependent relaxation (EDR), 5) lipid metabolism, and 6) pharmacological treatment against ischemia-induced mechanism. Results were as follows.1) Persistent decrease in coronary venous oxygen saturation (>5%) during rapid atrial pacing was an early sign of ischemia in the CMD patients. 2) The CMD patients had hypokinetic wall motion on effort in the apical area of the left ventricle and showed patchy enhancement of sonicated albumin in the left ventricular myocardium during dipyridamole-induced ischemia, suggesting coronary steal phenomenon. 3) There were no differences in arterial and venous adenosine concentrations during ischemia between CMD and control subjects. 4) The EDR of coronary microvessels in the CMD patients was significantly lower than that in the control subjects, although coronary conduit EDR was similar in these 2 groups. 5) There were no differences in T-chol, HDL-chol and LDL-chol between CMD and control subjects. Howeber, serum oxidized LDL was significantly higher in the CMD than in the control subjects. 6) Aminophylline and ACE inhibitor lessened ECG ST-dep during exercise in the CMD patients. Especially, a long-term administration (3 months) of ACE inhibitor appeared to reduce not only ECG ST-dep but also subjective complaints in the CMD patients. These results imply that oxidized LDL may impair endothelium of coronary prearteriolar vessel specifically, resulting in microvascular ischemia via coronary steal phenomenon. In conclusion, we assume that ACE inhibitor is effective for treatment of the patients with CMD.