Pharmacologic activation of the human coronary microcirculation in vitro: endothelium-dependent dilation and differential responses to acetylcholine
Pharmacologic activation of the human coronary microcirculation in vitro: endothelium-dependent dilation and differential responses to acetylcholine
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DOI：
10.1016/s0008-6363(98)00035-2
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发表时间：
1998-06-01
影响因子：
10.8
通讯作者：
Gutterman, DD
中科院分区：
文献类型：
--
作者：
Miller, FJ;Dellsperger, KC;Gutterman, DD
目的：人体冠状动脉阻力循环的体内研究不能控制心肌代谢、压迫和神经体液影响的间接影响。本研究直接检测了人类冠状动脉微循环对受体依赖性和非依赖性激动剂的血管扩张反应。方法：分离体外循环时获得的人右心房附件（直径103 +/- 2 μ m， n = 185支血管，来自145例患者）的心房小动脉和移植心脏的左心室血管（直径148 +/- 10 μ m， n = 57支血管，来自18例患者）。解剖后，在Kreb缓冲液中，在零流量条件下，在60 mmHg的恒定膨胀压力下，将血管安装在移液器上。外施药物，用视频显微镜测量直径的稳态变化。结果：内皮素或自发张力收缩后，二磷酸腺苷（ADP）浓度的增加在心房（最大89 +/- 4%，n = 76）和心室（最大74 +/- 9%，n = 10）血管中产生类似的剂量依赖性扩张。机械去除内皮细胞可消除ADP的扩张。心房和心室对缓激肽、P物质、花生四烯酸和钙离子包体A23187均有类似的扩张剂反应。相比之下，乙酰胆碱（ACh）收缩所有心房血管（-58 +/- 3%,n = 63），与患者年龄或基础疾病无关。这种收缩被剥蚀所减弱，但不受一氧化氮合酶或环加氧酶抑制的影响。从人心室分离的微血管对乙酰胆碱表现出异质反应，其中扩张是主要反应。结论：我们的结论是，分离的人冠状动脉表现出内皮依赖性扩张。然而，对乙酰胆碱的反应是独特的心房血管收缩和心室小动脉扩张。(C) 1998 Elsevier Science B.V.版权所有
Objectives: In vivo studies of the human coronary resistance circulation cannot control for indirect effects of myocardial metabolism, compression, and neurohumoral influences. This study directly examined the vasodilator responses of the human coronary microcirculation to both receptor-dependent and -independent agonists. Methods: Atrial arterioles were dissected from human right atrial appendage (103 +/- 2 mu m diameter, n = 185 vessels from 145 patients) obtained at the time of cardiopulmonary bypass and left ventricular vessels from explanted human hearts (148 +/- 10 mu m diameter, n = 57 vessels from 18 patients). After dissection, vessels were mounted onto pipettes in Kreb's buffer under conditions of zero flow and at a constant distending pressure of 60 mmHg. Drugs were applied extraluminally and steady state changes in diameter measured with videomicroscopy. Results: After contraction by endothelin or spontaneous tone, increasing concentrations of adenosine diphosphate (ADP) produced a similar dose-dependent dilation in vessels from atria (maximum 89 +/- 4%, n = 76) and ventricles (maximum 74 +/- 9%, n = 10). The dilation to ADP was abolished by mechanical removal of the endothelium. Similar dilator responses were found to bradykinin, substance P, arachidonic acid, and the calcium ionophore A23187 in both atria and ventricle. In contrast, acetylcholine (ACh) constricted all atrial vessels (-58 +/- 3%, n = 63) regardless of patient age or underlying disease. This constriction was attenuated by denudation, but not affected by inhibition of nitric oxide synthase or cyclo-oxygenase. Microvessels isolated from human ventricle exhibited a heterogeneous response to ACh with dilation being the predominant response. Conclusions: We conclude that isolated human coronary arterioles demonstrate endothelium-dependent dilation. However, the response to acetylcholine is unique with vasoconstriction in atrial vessels and dilation in ventricular arterioles. (C) 1998 Elsevier Science B.V. All rights reserved.