西地那非和降钙素基因相关肽可扩张硬脊膜内动脉：3T MR 血管造影在健康志愿者中的研究。

Sildenafil and calcitonin gene-related peptide dilate intradural arteries: A 3T MR angiography study in healthy volunteers.

机构信息

1 Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

2 Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Cephalalgia. 2019 Feb;39(2):264-273. doi: 10.1177/0333102418787336. Epub 2018 Jul 5.

DOI:10.1177/0333102418787336

PMID:29976087

Abstract

BACKGROUND

Sildenafil and calcitonin gene-related peptide are vasoactive substances that induce migraine attacks in patients. The intradural arteries are thought to be involved, but these have never been examined in vivo. Sildenafil is the only migraine-inducing compound for which cephalic, extracranial artery dilation is not reported. Here, we investigate the effects of sildenafil and calcitonin gene-related peptide on the extracranial and intradural parts of the middle meningeal artery.

METHODS

In a double-blind, randomized, three-way crossover, placebo-controlled head-to-head comparison study, MR-angiography was recorded in healthy volunteers at baseline and twice after study drug (sildenafil/ calcitonin gene-related peptide/saline) administration. Circumferences of extracranial and intradural middle meningeal artery segments were measured using semi-automated analysis software. The area under the curve for circumference change was compared using paired t-tests between study days.

RESULTS

Twelve healthy volunteers completed the study. The area under the curve was significantly larger on both the sildenafil and the calcitonin gene-related peptide day in the intradural middle meningeal artery (calcitonin gene-related peptide, p = 0.013; sildenafil, p = 0.027) and the extracranial middle meningeal artery (calcitonin gene-related peptide, p = 0.0003; sildenafil, p = 0.021), compared to placebo. Peak intradural middle meningeal artery dilation was 9.9% (95% CI [2.9-16.9]) after sildenafil (T) and 12.5% (95% CI [8.1-16.8]) after calcitonin gene-related peptide (T). Peak dilation of the extracranial middle meningeal artery after calcitonin gene-related peptide (T) was 15.7% (95% CI [11.2-20.1]) and 18.9% (95% CI [12.8-24.9]) after sildenafil (T).

CONCLUSION

An important novel finding is that both sildenafil and calcitonin gene-related peptide dilate intradural arteries, supporting the notion that all known pharmacological migraine triggers dilate cephalic vessels. We suggest that intradural artery dilation is associated with headache induced by calcitonin gene-related peptide and sildenafil.

摘要

背景

西地那非和降钙素基因相关肽是引起偏头痛发作的血管活性物质，被认为与颅内动脉有关，但这些物质在体内从未被检查过。西地那非是唯一一种引起偏头痛的化合物，其不会引起颅外动脉扩张。在这里，我们研究了西地那非和降钙素基因相关肽对硬脑膜中动脉颅外和颅内部分的影响。

方法

在一项双盲、随机、三向交叉、安慰剂对照的头对头比较研究中，在基线和研究药物（西地那非/降钙素基因相关肽/生理盐水）给药后两次记录健康志愿者的磁共振血管造影。使用半自动分析软件测量颅外和颅内硬脑膜中动脉节段的周长。使用配对 t 检验比较研究日之间周长变化的曲线下面积。

结果

12 名健康志愿者完成了研究。在颅内硬脑膜中动脉（降钙素基因相关肽，p=0.013；西地那非，p=0.027）和颅外硬脑膜中动脉（降钙素基因相关肽，p=0.0003；西地那非，p=0.021）中，西地那非和降钙素基因相关肽日的曲线下面积明显大于安慰剂日。西地那非后颅内硬脑膜中动脉扩张峰值为 9.9%（95%CI [2.9-16.9]），降钙素基因相关肽后为 12.5%（95%CI [8.1-16.8]）。降钙素基因相关肽（T）后颅外硬脑膜中动脉扩张峰值为 15.7%（95%CI [11.2-20.1]），西地那非（T）后为 18.9%（95%CI [12.8-24.9]）。