Spiess B D, Cochran R P
Department of Anesthesiology, University of Washington, Seattle 98195, USA.
J Cardiothorac Vasc Anesth. 1996 Jan;10(1):83-89; quiz 89-90. doi: 10.1016/s1053-0770(96)80182-0.
Artificial blood has been sought for a considerable period of time and two major lines of research have led to FDA testing of some possible compounds. The two major types of compounds are polymerized hemoglobin moieties and perfluorocarbon emulsions (PFC). Polymerized hemoglobin preparations have the ability to carry oxygen and release it in a manner similar to the oxyhemoglobin dissociation curve of whole blood. PFCs carry oxygen, nitrogen and carbon dioxide, as well as all other non-polar gases, by enhanced chemical solubility. Therefore, all dissolved gases are available for metabolic utilization and no sinusoidal release curve of oxygen is encountered. Early PFC emulsions had problems with toxicity of the emulsifier and were difficult to get into their emulsion for infusion. Furthermore they were very dilute in the active ingredient for gas transport. Today there are second generation PFCs becoming available that have a 40% concentration of the PFC and therefore the potential for gas transport is greatly increased. The PFC emulsions have a very small size, 0.1 microns, so the surface for gas exchange is massively increased as well as the potential increased for perfusion into areas of potentially sludged erythrocytes. Work with the PFCs has shown them now to be able to carry adequate oxygen to work as blood substitutes. They have shown protection from air embolism in a number of animal and end-organ models. What makes the PFCs unique is their ability to carry/absorb nitrogen and therefore protect from gas embolization. There are data in animal models showing significant cerebral protection in cardiopulmonary bypass models. The new PFCs should sometime in the not-too-distant future be tested in human bypass with assessments of neuropsychiatric dysfunction and stroke.
人们寻找人造血液已经有相当长的一段时间了,两条主要的研究路线已导致美国食品药品监督管理局(FDA)对一些可能的化合物进行测试。这两种主要类型的化合物是聚合血红蛋白部分和全氟碳乳液(PFC)。聚合血红蛋白制剂有携带氧气并以类似于全血氧合血红蛋白解离曲线的方式释放氧气的能力。全氟碳通过增强化学溶解性来携带氧气、氮气、二氧化碳以及所有其他非极性气体。因此,所有溶解的气体都可用于代谢利用,并且不会遇到氧气的正弦释放曲线。早期的全氟碳乳液存在乳化剂毒性问题,并且难以制成可用于输注的乳液。此外,它们在用于气体运输的活性成分方面非常稀释。如今,有第二代全氟碳产品可供使用,其全氟碳浓度为40%,因此气体运输的潜力大大增加。全氟碳乳液的尺寸非常小,为0.1微米,所以气体交换的表面积大幅增加,灌注到潜在红细胞淤滞区域的可能性也增加了。对全氟碳的研究表明,它们现在能够携带足够的氧气来充当血液替代品。在许多动物和终末器官模型中,它们已显示出对空气栓塞有保护作用。全氟碳的独特之处在于其携带/吸收氮气的能力,从而防止气体栓塞。动物模型中有数据表明在体外循环模型中对大脑有显著的保护作用。在不久的将来,新型全氟碳应该会在人体体外循环中进行测试,并评估神经精神功能障碍和中风情况。