体外人冠状动脉微循环的药理学激活：内皮依赖性舒张及对乙酰胆碱的不同反应

Pharmacologic activation of the human coronary microcirculation in vitro: endothelium-dependent dilation and differential responses to acetylcholine.

作者信息

Miller F J, Dellsperger K C, Gutterman D D

机构信息

Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA.

出版信息

Cardiovasc Res. 1998 Jun;38(3):744-50. doi: 10.1016/s0008-6363(98)00035-2.

DOI:10.1016/s0008-6363(98)00035-2

PMID:9747443

Abstract

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 microns diameter, n = 185 vessels from 145 patients) obtained at the time of cardiopulmonary bypass and left ventricular vessels from explanted human hearts (148 +/- 10 microns 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.

摘要

目的

人体冠状动脉阻力循环的体内研究无法控制心肌代谢、压迫及神经体液影响的间接效应。本研究直接检测了人体冠状动脉微循环对受体依赖性和非依赖性激动剂的血管舒张反应。

方法

在体外循环时获取人右心耳的心房小动脉（直径103±2微米，来自145例患者的185条血管），以及取自离体人心脏的左心室血管（直径148±10微米，来自18例患者的57条血管）。解剖后，将血管置于含Krebs缓冲液的移液管上，零流量条件下，恒定扩张压力为60 mmHg。药物经管腔外给药，通过视频显微镜测量直径的稳态变化。

结果

在内皮素收缩或自发张力后，随着二磷酸腺苷（ADP）浓度增加，心房血管（最大扩张89±4%，n = 76）和心室血管（最大扩张74±9%，n = 10）出现相似的剂量依赖性扩张。机械去除内皮后，对ADP的扩张作用消失。心房和心室对缓激肽、P物质、花生四烯酸及钙离子载体A23187有相似的舒张反应。相比之下，乙酰胆碱（ACh）使所有心房血管收缩（-58±3%，n = 63），与患者年龄或基础疾病无关。这种收缩在剥脱内皮后减弱，但不受一氧化氮合酶或环氧化酶抑制的影响。从人心室分离的微血管对ACh表现出异质性反应，以扩张为主。