A new rodent model of cerebral hyperperfusion

Background: 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. Methods: 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. Results: 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. Conclusions: 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.