Silav Gökalp, Ergün Hakan, Dolgun Habibullah, Sancak Tanzer, Sargon Mustafa F, Egemen Nihat
Department of Neurosurgery, Faculty of Medicine, Medipol University, Istanbul, Turkey -
Department of Pharmacology, Faculty of Medicine, Ankara University, Ankara, Turkey.
J Neurosurg Sci. 2017 Aug;61(4):380-387. doi: 10.23736/S0390-5616.16.03068-X. Epub 2014 Nov 4.
The purpose of this study was to evaluate the effect of the systemic administration of dipyrone in a triple subarachnoid hemorrhage (SAH) model of cerebral vasospasm in rabbits.
Experimental subarachnoid hemorrhage was induced in rabbits by injecting autologous arterial blood into the cisterna magna. Digital subtraction angiographies (DSA) were performed before and after the first experimental SAH, and at 30, 45, 60 minutes and 72 hours after the first drug administration to measure the diameter of basilar artery. Intracisternal blood injections were repeated 24 and 48 hours after the first injection. Dipyrone (N.=20) or 0.9% NaCl (N.=20) was administered intravenously after initial SAH induction and repeated at 8-hour intervals intramuscularly. After sacrificing by perfusion-fixation, basilar arteries were removed and sectioned for transmission electron microscopic (TEM) examination.
The average basilar artery diameter measured by DSA was 724±19 μm in the control, and 686±29 μm in treatment group before SAH. After SAH, mean basilar artery diameters decreased to 71% and 68% of their basal values, respectively. Dipyrone significantly attenuated the basilar artery diameter at one and 72 hours after the first drug administration, in comparison to the control group. TEM studies showed more edema in the endothelial cells of the basilar arteries of the control group when compared to the treatment group.
Dipyrone showed a beneficial effect in autologous blood-induced basilar artery vasospasm in rabbits. These data support the idea that dipyrone can be a potential candidate drug to be tested in patients suffering from cerebral vasospasm secondary to subarachnoid hemorrhage.
本研究旨在评估在兔三重蛛网膜下腔出血(SAH)脑血管痉挛模型中全身应用安乃近的效果。
通过向兔小脑延髓池注射自体动脉血诱导实验性蛛网膜下腔出血。在首次实验性SAH前后、首次给药后30、45、60分钟和72小时进行数字减影血管造影(DSA),以测量基底动脉直径。在首次注射后24和48小时重复小脑延髓池内血液注射。首次SAH诱导后静脉注射安乃近(N = 20)或0.9%氯化钠(N = 20),并在8小时间隔后肌肉重复给药。灌注固定处死动物后,取出基底动脉并切片进行透射电子显微镜(TEM)检查。
SAH前,DSA测量的对照组基底动脉平均直径为724±19μm,治疗组为686±29μm。SAH后,基底动脉平均直径分别降至其基础值的71%和68%。与对照组相比,安乃近在首次给药后1小时和72小时显著减轻了基底动脉直径。TEM研究显示,与治疗组相比,对照组基底动脉内皮细胞水肿更明显。
安乃近对兔自体血诱导的基底动脉血管痉挛显示出有益作用。这些数据支持安乃近可作为蛛网膜下腔出血继发脑血管痉挛患者潜在候选药物进行试验的观点。