酮色林对稳定型心绞痛患者、变异型心绞痛患者及对照患者冠状动脉近端和远端对冠脉内注射5-羟色胺的收缩反应的影响。

Effect of ketanserin on proximal and distal coronary constrictor responses to intracoronary infusion of serotonin in patients with stable angina, patients with variant angina, and control patients.

作者信息

McFadden E P, Bauters C, Lablanche J M, Leroy F, Clarke J G, Henry M, Schandrin C, Davies G J, Maseri A, Bertrand M E

机构信息

Service de Cardiologie B et Hémodynamique, Hôpital Cardiologique, Lille, France.

出版信息

Circulation. 1992 Jul;86(1):187-95. doi: 10.1161/01.cir.86.1.187.

DOI:10.1161/01.cir.86.1.187

PMID:1617772

Abstract

BACKGROUND

Serotonin, released by aggregating platelets, may contribute to or cause myocardial ischemia by constricting epicardial vessels. Experimental studies suggest that this constriction is mediated by two distinct serotonin receptor subtypes: 5-hydroxytryptamine1-like (S1-like) and 5-hydroxytryptamine2 (S2).

METHODS AND RESULTS

To determine the relative contribution of S1-like and S2 receptors to the vasoconstrictor effects of serotonin, we studied the effect of ketanserin (0.75 mg, intracoronary), a selective S2 receptor antagonist, on the constrictor response of human coronary vessels to intracoronary infusions of serotonin. In control patients (n = 7), serotonin (10(-4) mol/l) caused significant (p less than 0.05) constriction only in distal segments, which was significantly (p less than 0.05) inhibited by ketanserin. In stable angina patients (n = 8), serotonin (10(-4) mol/l) caused significant constriction in proximal (p less than 0.01) and distal (p less than 0.01) segments, which was significantly inhibited by ketanserin in proximal (p less than 0.05) but not distal (p = 0.30) segments. In patients with variant angina (n = 3), epicardial occlusion at the site of preexisting stenoses in proximal locations occurred at infused concentrations of 10(-6) (one patient) or 10(-5) (two patients) mol/l. The infusion of the same concentration of serotonin after ketanserin again caused epicardial occlusion.

CONCLUSIONS

Our results suggest that functionally important S1-like receptors that mediate vasoconstriction exist in the epicardial vessels of patients with stable or variant angina. Their activation, either at hyperreactive sites in patients with variant angina or in the distal epicardial vessels of patients with chronic stable angina, may contribute to or cause myocardial ischemia when serotonin is released after the intracoronary activation of platelets.

摘要

背景

聚集的血小板释放的血清素可能通过收缩心外膜血管导致或促成心肌缺血。实验研究表明，这种收缩是由两种不同的血清素受体亚型介导的：5-羟色胺1样（S1样）和5-羟色胺2（S2）。

方法与结果

为了确定S1样和S2受体对血清素血管收缩作用的相对贡献，我们研究了选择性S2受体拮抗剂酮色林（0.75毫克，冠状动脉内给药）对人冠状动脉对冠状动脉内输注血清素的收缩反应的影响。在对照患者（n = 7）中，血清素（10⁻⁴摩尔/升）仅在远端节段引起显著（p < 0.05）收缩，酮色林可显著（p < 0.05）抑制该收缩。在稳定型心绞痛患者（n = 8）中，血清素（10⁻⁴摩尔/升）在近端（p < 0.01）和远端（p < 0.01）节段均引起显著收缩，酮色林在近端节段（p < 0.05）可显著抑制该收缩，但在远端节段（p = 0.30）则无此作用。在变异型心绞痛患者（n = 3）中，在近端部位预先存在狭窄处，输注浓度为10⁻⁶（1例患者）或10⁻⁵（2例患者）摩尔/升的血清素时发生心外膜闭塞。在给予酮色林后输注相同浓度的血清素再次导致心外膜闭塞。