Hosaka T, Yamamoto Y L, Diksic M
Cone Neurosurgical Research Laboratory, Montreal Neurological Institute, McGill University, Quebec, Canada.
Stroke. 1991 Dec;22(12):1562-6. doi: 10.1161/01.str.22.12.1562.
For treatment of acute stroke, drug therapy administered systemically has been unreliable due to inadequate delivery of drug into ischemic tissue. We have developed a new method to deliver drugs into the ischemic tissue by retrograde perfusion of the cerebral vein.
We examined in rats the effectiveness of administering verapamil into ischemic tissue by retrograde perfusion through the cerebral vein, starting 3 hours after occlusion of the middle cerebral artery. Twenty-four Fischer-344 rats with occlusion of the middle cerebral artery were divided into four groups of six rats each. Group A rats had no treatment, group B rats received verapamil intravenously, and groups C and D rats received verapamil by transvenous perfusion of the brain with blood and with saline, respectively. We studied local cerebral blood flow using the autoradiographic method with carbon-14-labeled iodoantipyrine and examined cerebral infarct volume with cresyl violet and Luxol fast blue staining.
As compared with group A rats, in groups C and D rats we found a significant and extensive increase of cerebral blood flow in the ischemic cortical and subcortical areas (55-119%, p less than 0.05) and a significant reduction of cerebral infarct volume (31-39%, p less than 0.05). We found no significant changes in group B rats.
This study shows that transvenous perfusion of the brain with verapamil starting 3 hours after occlusion of the middle cerebral artery produces a significantly beneficial effect in rats.
对于急性中风的治疗，由于药物向缺血组织的递送不足，全身给药治疗一直不可靠。我们开发了一种通过脑静脉逆行灌注将药物递送至缺血组织的新方法。
在大鼠中，我们研究了在大脑中动脉闭塞3小时后通过脑静脉逆行灌注将维拉帕米给予缺血组织的有效性。将24只大脑中动脉闭塞的Fischer-344大鼠分为四组，每组6只。A组大鼠不接受治疗，B组大鼠静脉注射维拉帕米，C组和D组大鼠分别用血液和生理盐水经静脉灌注大脑给予维拉帕米。我们使用碳-14标记的碘安替比林的放射自显影方法研究局部脑血流量，并用甲酚紫和卢戈氏坚牢蓝染色检查脑梗死体积。
与A组大鼠相比，在C组和D组大鼠中，我们发现缺血皮质和皮质下区域的脑血流量显著且广泛增加（55 - 119%，p < 0.05），脑梗死体积显著减小（31 - 39%，p < 0.05）。在B组大鼠中未发现显著变化。
本研究表明，在大脑中动脉闭塞3小时后经静脉灌注维拉帕米对大鼠产生显著有益效果。
