Pathophysiological evaluation and treatment of coronary microvessel disorders in humans

人类冠状动脉微血管疾病的病理生理学评估和治疗

• 批准号: 06670686
• 负责人: MIKUNIYA Atsushi
• 金额: $ 0.96万
• 依托单位: HIROSAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670686/
• 关键词: Coronary microvessel disorder; Myocardial ischemia; Coronary hemodynamics; Endothelium-dependent vasodilation; Oxidized LDL; ACE inhibitor; Exercise; 冠微小循環; 内皮障害; coronary steal; ACE阻害薬; coronary microcirculation; myocardial ischemia; endothe

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.

我们从1)如何发现缺血证据，2)冠状动脉血流动力学特征，3)腺苷动力学，4)内皮依赖性松弛(EDR)，5)脂代谢，6)抗缺血机制的药物治疗等方面对冠状动脉微血管紊乱(CMD)进行了研究。结果如下：1)快速心房起搏时冠状静脉血氧饱和度(&gt；5%)持续下降是CMD患者缺血的早期征象。2)在潘生丁诱导的心肌缺血过程中，CMD患者左心室心尖部运动减慢，左室心肌声学白蛋白呈片状强化，提示有冠状动脉盗血现象。3)脑缺血期CMD患者动脉和静脉中的腺苷浓度与对照组相比无明显差异。4)冠脉微血管EDR在CMD组明显低于对照组，而冠脉导管EDR在两组间差异无统计学意义。5)CMD患者血清总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇与正常对照组比较差异无统计学意义。然而，CMD患者的血清氧化低密度脂蛋白水平明显高于对照组。6)氨茶碱和血管紧张素转换酶抑制剂可降低慢性心肌梗塞患者运动时的心电图ST段压低。尤其是长期服用ACE抑制剂(3个月)，似乎不仅能减少CMD患者的心电图ST-Dp，而且还能减少主观主诉。这些结果提示，氧化型低密度脂蛋白可能通过冠脉盗血现象特异性地损伤冠脉小动脉前血管内皮细胞，导致微血管缺血。综上所述，我们认为血管紧张素转换酶抑制剂对CMD患者是有效的。

项目成果

Narita T.: "Ventricular and coronary hemodynamic characteristic in patients with chest pain and ECG-ST depression during exercise despite normal coronary arteriograms." Hirosaki Med J. 46. 199-209 (1995)

Narita T.：“尽管冠状动脉造影正常，但运动期间出现胸痛和 ECG-ST 压低的患者的心室和冠状动脉血流动力学特征。”

Mikuniya A.: "Syndrome X and coronary microcirculation" Cardioangiology. 38. 268-274 (1995)

Mikuniya A.：“X 综合征和冠状动脉微循环”心血管病学。

Mikuniya A.: "Endothelium-dependent coronary vasodilation in humans." Therapeutic Research. 16. 128-133 (1995)

Mikuniya A.：“人类内皮依赖性冠状动脉舒张。”

三國谷 淳: "シンドロームXと冠微小循環" 循環器科. 38. 268-274 (1995)

Jun Mikuniya：“X 综合征和冠状动脉微循环”，心脏病学部，38. 268-274 (1995)。

三國谷,淳: "ヒト冠循環における血管内皮由来弛緩動態" Therapeutic Research. 16. 128-133 (1995)

Jun Mikuniya：“人体冠状循环中血管内皮衍生的松弛动力学”治疗研究。16. 128-133 (1995)。