Fagan S C, Bowes M P, Lyden P D, Zivin J A
Department of Pharmacy Practice, Wayne State University, Detroit, Michigan, USA.
Exp Neurol. 1998 Mar;150(1):153-8. doi: 10.1006/exnr.1997.6756.
We examined the relationship between acute hypertension following cerebral embolization and subsequent hemorrhagic transformation (HT) in a rabbit embolic stroke model. We have shown previously that the likelihood and severity of hemorrhage were significantly correlated with the magnitude of an acute hypertensive response to embolization. It was not clear, however, whether hypertension actually caused hemorrhage or was merely a marker of more severe stroke. In the current studies, we attempted to clarify the relationship between acute hypertension and HT by either pharmacologically inducing or attenuating the brief hypertensive response to embolization in rabbits. Under halothane anesthesia, two catheters were implanted in the right carotid arteries of male New Zealand white rabbits, one oriented toward the heart and one toward the brain. The animals were allowed to awaken and were embolized using blood clot emboli injected into the middle cerebral artery. Blood pressure was monitored via the second carotid catheter. In the first experiment, hypertension was induced with angiotensin II, administered at the time of embolization or 1 h later. In the second experiment, we attempted to attenuate the hypertensive response using intravenous labetalol. The animals were sacrificed 18 h after embolization and the brains evaluated for hemorrhage. In the first experiment, administration of angiotensin II immediately after embolization did not increase the hypertensive response to embolization further than that spontaneously occurring, and no angiotensin II-related HT was observed. In contrast, an additional angiotensin-II-induced hypertensive episode 1 h after embolization significantly increased the number of 5-mm serial brain sections displaying HT, from 3.0 +/- .3 (mean +/- SE) in Controls to 5.4 +/- .8 in treated animals. In the second experiment, administration of labetalol (15 mg/kg) significantly reduced the number of brain sections with visible HT, from 3.2 +/- .5 in controls to 1.6 +/- .4 in treated animals. Acute hypertension during the first hour after cerebral embolization promotes HT in this rabbit embolic stroke model. Labetalol prevents blood pressure elevation and reduces the extent of HT in the same model.
我们在兔栓塞性中风模型中研究了脑栓塞后急性高血压与随后出血性转化（HT）之间的关系。我们之前已经表明，出血的可能性和严重程度与栓塞后急性高血压反应的幅度显著相关。然而，尚不清楚高血压是实际导致了出血还是仅仅是更严重中风的一个标志。在当前的研究中，我们试图通过药理学方法诱导或减弱兔对栓塞的短暂高血压反应来阐明急性高血压与HT之间的关系。在氟烷麻醉下，将两根导管植入雄性新西兰白兔的右颈动脉，一根朝向心脏，一根朝向大脑。让动物苏醒后，通过向大脑中动脉注射血凝块栓子进行栓塞。通过第二根颈动脉导管监测血压。在第一个实验中，在栓塞时或1小时后给予血管紧张素II诱导高血压。在第二个实验中，我们试图使用静脉注射拉贝洛尔减弱高血压反应。栓塞后18小时处死动物，并对大脑进行出血评估。在第一个实验中，栓塞后立即给予血管紧张素II并没有比自发出现的情况进一步增加对栓塞的高血压反应，并且未观察到与血管紧张素II相关的HT。相比之下，栓塞后1小时额外出现的血管紧张素II诱导的高血压发作显著增加了显示HT的5毫米连续脑切片数量，从对照组的3.0±0.3（平均值±标准误）增加到治疗组动物的5.4±。在第二个实验中，给予拉贝洛尔（15毫克/千克）显著减少了有可见HT的脑切片数量，从对照组的3.2±0.5减少到治疗组动物的1.6±0.4。在这个兔栓塞性中风模型中，脑栓塞后第一小时的急性高血压促进了HT。拉贝洛尔可防止血压升高并减少同一模型中HT的程度。
