Stanworth P A, Dutton J, Paul K S, Fawcett R, Whalley E
University Department of Neurosurgery, Manchester Royal Infirmary, U.K.
Acta Neurochir Suppl (Wien). 1988;42:85-7. doi: 10.1007/978-3-7091-8975-7_17.
One of the major problems associated with the treatment of ruptured intracranial aneurysms is the syndrome of late onset ischaemia. Patients so affected deteriorate neurologically and cerebral angiography often shows narrowing of the intracranial arteries, commonly known as vasospasm. Many drugs have been used to treat the condition but with little success. A new group of compounds have come into clinical use recently, the Prostaglandins. One member, Prostacyclin (PGI2 or Epoprostenol) is claimed to be one of the most potent vasodilators known. It was used at Manchester first on an experimental model. An isolated piece of human basilar artery was caused to contract using various agents. Prostacyclin was then used in an attempt to relax the contracted segment of artery. It, surprisingly, caused profound relaxation at very low concentrations of Prostacyclin, yet at higher concentrations it again caused the artery to contract. A literature search suggested this also was seen in the living subject and the crossover occurred at a dosage of 5 ng/kg/min. A limited pilot trial was therefore devised using Prostacyclin at the low concentration of 1 ng/kg/min and used on six patients. Patients were assessed, in the main, for clinical improvement and change in radiological spasm. Clinically, the results exceeded our expectations in that all patients improved, some back to normal. Radiologically, the vasospasm changed but did not revert completely and also unusual extracranial-intracranial anastomoses appeared in the angiograms. In addition, in one patient, cerebral blood flow showed a more than threefold increase. No generalised cardiovascular collapse occurred and no bleeding tendency was observed.
与破裂颅内动脉瘤治疗相关的主要问题之一是迟发性缺血综合征。受此影响的患者神经功能会恶化,脑血管造影常显示颅内动脉狭窄,即通常所说的血管痉挛。许多药物已被用于治疗这种情况,但收效甚微。最近有一类新的化合物进入临床应用,即前列腺素。其中一种成员前列环素(PGI2或依前列醇)据称是已知最强效的血管扩张剂之一。它最早在曼彻斯特用于一个实验模型。使用各种药剂使一段分离的人基底动脉收缩。然后使用前列环素试图使收缩的动脉段松弛。令人惊讶的是,在非常低的前列环素浓度下它就引起了深度松弛,但在较高浓度时它又使动脉再次收缩。文献检索表明在活体中也观察到了这种情况,转变发生在5纳克/千克/分钟的剂量时。因此设计了一项有限的试点试验,使用浓度为1纳克/千克/分钟的前列环素,应用于6名患者。主要对患者的临床改善情况和放射学上的痉挛变化进行评估。在临床上,结果超出了我们的预期,因为所有患者都有改善,一些恢复到了正常状态。在放射学上,血管痉挛有变化但没有完全恢复,而且血管造影中还出现了不寻常的颅外-颅内吻合。此外,在一名患者中,脑血流量增加了三倍多。没有发生全身性心血管衰竭,也未观察到出血倾向。