Abutarboush Rania, Aligbe Chioma, Pappas Georgina, Saha Biswajit, Arnaud Francoise, Haque Ashraful, Auker Charles, McCarron Richard, Scultetus Anke, Moon-Massat Paula
NeuroTrauma Department, Naval Medical Research Center (NMRC), Silver Spring, MD 20910, USA.
J Funct Biomater. 2014 Nov 18;5(4):246-58. doi: 10.3390/jfb5040246.
The use of hemoglobin-based oxygen carriers (HBOC) as oxygen delivering therapies during hypoxic states has been hindered by vasoconstrictive side effects caused by depletion of nitric oxide (NO). OxyVita C is a promising oxygen-carrying solution that consists of a zero-linked hemoglobin polymer with a high molecular weight (~17 MDa). The large molecular weight is believed to prevent extravasation and limit NO scavenging and vasoconstriction. The aim of this study was to assess vasoactive effects of OxyVita C on systemic blood pressures and cerebral pial arteriole diameters. Anesthetized healthy rats received four intravenous (IV) infusions of an increasing dose of OxyVita C (2, 25, 50, 100 mg/kg) and hemodynamic parameters and pial arteriolar diameters were measured pre- and post-infusion. Normal saline was used as a volume-matched control. Systemic blood pressures increased (P ≤ 0.05) with increasing doses of OxyVita C, but not with saline. There was no vasoconstriction in small (<50 µm) and medium-sized (50-100 µm) pial arterioles in the OxyVita C group. In contrast, small and medium-sized pial arterioles vasoconstricted in the control group. Compared to saline, OxyVita C showed no cerebral vasoconstriction after any of the four doses evaluated in this rat model despite increases in blood pressure.
基于血红蛋白的氧载体（HBOC）在缺氧状态下作为氧输送疗法的应用，一直受到一氧化氮（NO）耗竭引起的血管收缩副作用的阻碍。OxyVita C是一种有前景的携氧溶液，由一种高分子量（约17 MDa）的零连接血红蛋白聚合物组成。据信，大分子量可防止血管外渗，并限制NO清除和血管收缩。本研究的目的是评估OxyVita C对全身血压和软脑膜小动脉直径的血管活性作用。对麻醉的健康大鼠进行四次静脉注射（IV），剂量递增的OxyVita C（2、25、50、100 mg/kg），并在注射前和注射后测量血流动力学参数和软脑膜小动脉直径。使用生理盐水作为体积匹配的对照。随着OxyVita C剂量的增加，全身血压升高（P≤0.05），但生理盐水注射后血压未升高。OxyVita C组中小（<50 µm）和中等大小（50 - 100 µm）的软脑膜小动脉没有血管收缩。相比之下，对照组中小和中等大小的软脑膜小动脉发生了血管收缩。与生理盐水相比，在该大鼠模型中评估的四剂中的任何一剂后，尽管血压升高，但OxyVita C均未显示出脑血管收缩。
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