Anesthesia Center for Critical Care Research, Department of Anesthesia, Wellman Center of Photomedicine, Boston, Massachusetts, USA.
Anesthesiology. 2010 Mar;112(3):586-94. doi: 10.1097/ALN.0b013e3181cd7838.
To date, there is no safe and effective hemoglobin-based oxygen carrier (HBOC) to substitute for erythrocyte transfusion. It is uncertain whether a deficiency of endothelial nitric oxide bioavailability (endothelial dysfunction) prevents or augments HBOC-induced vasoconstriction.
Hemodynamic effects of infusion of PolyHeme (1.08 g hemoglobin/kg; Northfield Laboratories, Evanston, IL) or murine tetrameric hemoglobin (0.48 g hemoglobin/kg) were determined in awake healthy lambs, awake mice, and anesthetized mice. In vitro, a cumulative dose-tension response was obtained by sequential addition of PolyHeme or tetrameric hemoglobin to phenylephrine-precontracted murine aortic rings.
Infusion of PolyHeme did not cause systemic hypertension in awake lambs but produced acute systemic and pulmonary vasoconstriction. Infusion of PolyHeme did not cause systemic hypertension in healthy wild-type mice but induced severe systemic vasoconstriction in mice with endothelial dysfunction (either db/db mice or high-fat fed wild-type mice for 4-6 weeks). The db/db mice were more sensitive to systemic vasoconstriction than wild-type mice after the infusion of either tetrameric hemoglobin or PolyHeme. Murine aortic ring studies confirmed that db/db mice have an impaired response to an endothelial-dependent vasodilator and an enhanced vasoconstrictor response to HBOC.
Reduction in low molecular weight hemoglobin concentrations to less than 1% is insufficient to abrogate the vasoconstrictor effects of HBOC infusion in healthy awake sheep or in mice with reduced vascular nitric oxide levels associated with endothelial dysfunction. These findings suggest that testing HBOCs in animals with endothelial dysfunction can provide a more sensitive indication of their potential vasoconstrictor effects.
迄今为止，尚无安全有效的血红蛋白基氧载体（HBOC）替代红细胞输注。内皮一氧化氮生物利用度（内皮功能障碍）的缺乏是否会预防或加剧 HBOC 引起的血管收缩尚不确定。
在清醒的健康羔羊、清醒的小鼠和麻醉的小鼠中，测定 PolyHeme（1.08 g 血红蛋白/ kg；Northfield Laboratories，Evanston，IL）或鼠四聚体血红蛋白（0.48 g 血红蛋白/ kg）输注的血流动力学效应。在体外，通过向预先用苯肾上腺素预收缩的鼠主动脉环中依次添加 PolyHeme 或四聚体血红蛋白来获得累积剂量-张力反应。
PolyHeme 输注不会引起清醒羔羊的全身性高血压，但会引起急性全身和肺血管收缩。PolyHeme 输注不会引起健康野生型小鼠的全身性高血压，但会引起内皮功能障碍的小鼠（4-6 周高脂喂养的 db/db 小鼠或野生型小鼠）严重的全身性血管收缩。与野生型小鼠相比，db/db 小鼠在输注四聚体血红蛋白或 PolyHeme 后对全身性血管收缩更为敏感。鼠主动脉环研究证实，db/db 小鼠对内皮依赖性血管扩张剂的反应受损，对 HBOC 的血管收缩反应增强。
将低分子量血红蛋白浓度降低到 1%以下不足以消除 HBOC 输注在健康清醒绵羊或血管内皮一氧化氮水平降低（与内皮功能障碍相关）的小鼠中引起的血管收缩作用。这些发现表明，在内皮功能障碍的动物中测试 HBOC 可以更敏感地提示其潜在的血管收缩作用。
