Johnston B M, Saxena P R
Br J Pharmacol. 1978 Jul;63(3):541-9. doi: 10.1111/j.1476-5381.1978.tb07810.x.
1 The radioactive microsphere method was used to study the effects of ergotamine (5, 10 and 20 mug/kg, i.v.) on systemic and regional haemodynamic variables in chloralose-urethane anaesthetized cats. The influence of the drug was also studied on the number of 15 mum microspheres escaping entrapment in the head to emerge in the left external jugular vein.2 Ergotamine decreased the heart rate and cardiac output. Since arterial blood pressure remained unchanged, calculated total peripheral resistance increased.3 The regional distribution of cardiac output obtained with 15 mum microspheres agreed well with previous studies in cats where 25 mum spheres were used. The most pronounced difference was that in the present investigation more microspheres, apparently escaping through arteriovenous anastomoses (AVAs), were detected in the lungs than when larger spheres had been used.4 Coronary blood flow decreased, while uterine blood flow was increased by the drug. The microsphere content of the lungs, which receive the spheres not only via bronchial arteries but also via AVAs, was greatly reduced by all doses of ergotamine. Ergotamine did not influence tissue blood flow to other major organs such as the brain, kidneys, skin, liver, skeletal muscle or the gastrointestinal tract.5 In the 16 experiments, 0.46 +/- 0.05 (s.e. mean)% of the total microspheres injected (equivalent to 11.7 +/- 1.4% of microspheres detected in the left-side of the head) appeared within 2 min of microsphere injection into the left external jugular vein. The highest dose of ergotamine significantly reduced the shunting of the microspheres in the head.6 Since 15 mum microspheres are only likely to reach the lungs by passing into the venous circulation through large glomus-type AVAs, we conclude that ergotamine reduces the fraction of microspheres appearing in the lungs by causing strong vasoconstriction in the AVAs in the head.7 In conformity with the closure of head AVAs is the finding that ergotamine reduced the jugular venous Po(2) and O(2) saturation thereby increasing the A-V O(2) saturation difference.8 It is quite possible that decreased A-V shunting may be the prominent mechanism of the antimigraine action of the drug, since sudden opening of AVA's has been implicated in the pathophysiology of migraine-syndrome.
采用放射性微球法,研究了麦角胺(静脉注射,剂量分别为5、10和20微克/千克)对氯醛糖-乌拉坦麻醉猫的全身及局部血流动力学变量的影响。还研究了该药物对15微米微球在头部未被截留而出现于左颈外静脉的数量的影响。
麦角胺使心率和心输出量降低。由于动脉血压保持不变,计算得出的总外周阻力增加。
用15微米微球获得的心输出量区域分布与先前在猫身上使用25微米微球的研究结果非常吻合。最显著的差异是,在本研究中,与使用较大微球时相比,在肺部检测到更多显然通过动静脉吻合支(AVA)逸出的微球。
麦角胺使冠状动脉血流量减少,而使子宫血流量增加。肺部不仅通过支气管动脉而且通过AVA接收微球,所有剂量的麦角胺均使肺部的微球含量大幅降低。麦角胺对其他主要器官如脑、肾、皮肤、肝、骨骼肌或胃肠道的组织血流量没有影响。
在16次实验中,注入的微球总数的0.46±0.05(标准误均值)%(相当于在头部左侧检测到的微球的11.7±1.4%)在将微球注入左颈外静脉后2分钟内出现。最高剂量的麦角胺显著减少了微球在头部的分流。
由于15微米微球只有通过大型球样AVA进入静脉循环才可能到达肺部,我们得出结论,麦角胺通过引起头部AVA强烈血管收缩,减少了出现在肺部的微球比例。
与头部AVA关闭一致的是,发现麦角胺降低了颈静脉血氧分压(Po(2))和氧饱和度,从而增加了动静脉血氧饱和度差。
减少动静脉分流很可能是该药物抗偏头痛作用的主要机制,因为AVA突然开放与偏头痛综合征的病理生理学有关。