Jia Bin, Zhao Lei, Xiao Wei, Cai Bing, Wang Tian-Long, Li Dong-Guo
Department of Anesthesiology, Xuanwu Hospital, Capital Medical University Beijing, China.
Biomedical Engineering Institute of Capital Medical University Beijing 100069, China.
Int J Clin Exp Med. 2015 Oct 15;8(10):17441-50. eCollection 2015.
Most studies of hyperperfusion and hyperperfusion syndrome after carotid endarterectomy or carotid stenting are based on clinical observation or meta-analyses in patients, whereas there is little corresponding fundamental research since proper animal model that can reproduce phenotype stably is not available. Therefore, we developed a rat model in which the pathophysiologic process of hyperperfusion can be mimicked.
Global ischemia was induced by occluding bilateral common carotid arteries (BCAO) for 2 weeks. After that, the ligature was loosened to allow reperfusion. Phenylephrine was administered at concentrations of 10, 20, 30, 40, 50, 80, and 120 μg/mL for rapidly elevating blood pressure. Relative cerebral blood flow in relation to mean arterial pressure (MAP) was measured with Laser Doppler techniques. Sham animals underwent the same surgical operation but without artery-occlusion and received the same concentrations of phenylephrine.
Mild hypertension rapidly increased cerebral blood flow. Phenylephrine at different concentrations produced different effects on blood pressure. Hyperperfusion can be induced by phenylephrine at around 30 μg/mL, whereas phenylephrine at 80 μg/ml or higher induced arrhythmia and further cardiac dysfunction thus failed to induce hyperperfusion.
Our data suggest that 30-50 μg/mL phenylephrine mildly elevated MAP and cerebral blood flow to the level exceeding 100% of baseline. This hyperperfusion model possesses several advantages including high phenotype reproducibility, low experimental failure rate and low animal mortality rate. It can be applied to study carotid stenosis or ischemia/reperfusion injury in rats.
大多数关于颈动脉内膜切除术或颈动脉支架置入术后高灌注及高灌注综合征的研究是基于对患者的临床观察或荟萃分析，然而由于缺乏能够稳定再现该表型的合适动物模型，相应的基础研究很少。因此，我们开发了一种可以模拟高灌注病理生理过程的大鼠模型。
通过结扎双侧颈总动脉（BCAO）2周诱导全脑缺血。之后，松开结扎线以实现再灌注。以10、20、30、40、50、80和120μg/mL的浓度给予去氧肾上腺素以快速升高血压。采用激光多普勒技术测量与平均动脉压（MAP）相关的相对脑血流量。假手术动物接受相同的外科手术，但不进行动脉结扎，并给予相同浓度的去氧肾上腺素。
轻度高血压迅速增加脑血流量。不同浓度的去氧肾上腺素对血压产生不同影响。约30μg/mL的去氧肾上腺素可诱导高灌注，而80μg/ml或更高浓度的去氧肾上腺素会诱发心律失常并进一步导致心脏功能障碍，从而无法诱导高灌注。
我们的数据表明，30 - 50μg/mL的去氧肾上腺素可使MAP和脑血流量轻度升高至超过基线100%的水平。这种高灌注模型具有几个优点，包括高表型再现性、低实验失败率和低动物死亡率。它可用于研究大鼠的颈动脉狭窄或缺血/再灌注损伤。
