血管内机制参与白蛋白对急性脑缺血的保护效应

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Albumin Therapy Improves Local Vascular Dynamics in a Rat Model of Primary Microvascular Thrombosis

A Two-Photon Laser-Scanning Microscopy Study

Anitha Nimmagadda, MD; Hee-Pyoung Park, MD, PhD; Ricardo Prado, MD Myron D. Ginsberg, MD

From the Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami Miller School of Medicine, Miami, Fla, USA.

Background and Purpose— High-dose human albumin is robustly neuroprotective in preclinical ischemia models and is currently in phase III clinical trial for acute ischemic stroke. To explore the hypothesis that albumin’s protective effect is mediated in part by salutary intravascular mechanisms, we assessed microvascular hemodynamics in a model of laser-induced cortical arteriolar thrombosis.

Methods— The cortical microcirculation of anesthetized, physiologically monitored Sprague-Dawley rats was studied in vivo via a frontoparietal cranial window (intact dura) by two-photon laser-scanning microscopy after plasma-labeling with fluorescein-dextran. Focal thrombosis was produced in 30- to 50-祄 cortical arterioles by laser irradiation. Arteriolar flow velocity was measured repeatedly by line-scanning. At 30 minutes post-thrombosis, animals were treated with either human albumin, 2 g/kg, or with saline control.

Results— Baseline arteriolar flow velocity averaged 3.5±1.8 mm/s and was reduced to 10% to 13% of control values by laser-induced thrombosis, which also led to focal vasodilatation (mean, 49% above baseline diameter). Saline treatment at 30 minutes post-thrombosis failed to influence arteriolar flow velocity, which remained depressed at 10% to 22% of control throughout the subsequent 60- to 90-minute observation period. By contrast, albumin treatment induced a prompt rise in median flow velocity to 38% of control by 10 minutes post-treatment, and to 61% to 67% of control by 50 to 60 minutes.

Conclusions— High-dose albumin therapy induces a prompt, sustained improvement in microvascular hemodynamics distal to a cortical arteriolar thrombosis; these data support an important intravascular component to albumin’s protective effect in acute cerebral ischemia.

Stroke. 2008;39:198-204


背景及目的:大量人血白蛋白对临床前缺血模型有着稳固的神经保护作用,目前已处急性缺血性中风研究第3期的临床试验阶段.为了探究白蛋白保护效应部分由良性血管内机制所介导的假说,我们评估了激光激励皮质血管栓塞模型中的微血管血流动力学的改变.

结果:基线水平的小动脉血流速度平均为3.5±1.8 mm/s；激光产生血栓后,血流速度减少10%-30%对照值,同时血管扩张(平均扩张到基线直径的49%).血栓形成后30分钟,使用盐水治疗不能影响小动脉的血液流速,在接下来(栓塞30分钟后)的60-90分钟的观察期内,流速仍减少了10%-22%.而白蛋白则在治疗后10分钟内立即引起流速提升38%对照值,治疗50-60分钟后,引起流速提升61%-67%.

结论:大剂量白蛋白治疗迅速且持续的引起皮质末梢小血管等栓塞微血管内血流动力学的改善；这些数据支持了白蛋白对ACI保护作用有血管内效应成分参与.