Remy B, Deby-Dupont G, Lamy M
Department of Anaesthesia and Intensive Care Medicine, University of Liège, Belgium.
Br Med Bull. 1999;55(1):277-98. doi: 10.1258/0007142991902259.
The problems posed by transfusion of homologous blood have led to the development of substances able to replace the gas transporting properties of blood. Perfluorocarbons (PFCs) emulsions and modified haemoglobin (Hb) solutions have been developed for this goal and are now tested in clinical assays. PFCs are synthetic fluorinated hydrocarbons, capable of dissolving large quantities of oxygen (O2; without binding) at high inspired concentrations of O2, and of delivering this O2 to the tissues. They are administered as emulsions containing particles with a diameter of approximately 0.2 micron, capable of entering the microcirculation. They are eliminated unchanged by the lungs within several days. Fluosol-DA 20% was the first PFC emulsion used in clinical practice. Currently, Oxygent, a second generation PFC emulsion, is being evaluated in clinical studies. The PFCs are not blood substitutes, but rather a means to ensure tissue oxygenation during extreme haemodilution. Solutions of free Hb do not have the antigenic characteristics of the blood groups, and do not require compatibility testing. They are fully saturated with O2 at ambient FiO2. The Hbs used are derived from either human or bovine sources, or via recombinant DNA technology. In order to maintain satisfactory intravascular half-life and O2 affinity, the Hb molecules are modified by adding internal crosslinks, by polymerization, and/or by encapsulation. After promising animal studies, several of these modified Hb solutions are now being studied in Phase III clinical trials. Among them, diaspirin cross-linked haemoglobin (DCLHb) has been used in cardiac and orthopaedic surgery, and for resuscitation of traffic accident victims. The initial results of multicentre trials are now being analysed.
输注同源血所带来的问题促使了能够替代血液气体运输特性的物质的研发。全氟碳化物（PFCs）乳剂和改良血红蛋白（Hb）溶液就是为这一目标而研发的，目前正在进行临床试验。PFCs是合成的氟化烃，在高吸入氧浓度下能够溶解大量氧气（O2；不结合），并将这些氧气输送到组织中。它们以含有直径约为0.2微米颗粒的乳剂形式给药，这些颗粒能够进入微循环。它们在数天内通过肺部以原形排出。氟碳乳剂（Fluosol-DA 20%）是临床实践中使用的第一种PFC乳剂。目前，第二代PFC乳剂氧合素（Oxygent）正在临床研究中进行评估。PFCs不是血液替代品，而是在极端血液稀释期间确保组织氧合的一种手段。游离Hb溶液不具有血型的抗原特性，也不需要进行相容性检测。在环境FiO2下它们能完全被O2饱和。所使用的Hb来源于人或牛，或通过重组DNA技术获得。为了维持令人满意的血管内半衰期和O2亲和力，通过添加内部交联、聚合和/或包封对Hb分子进行改良。在动物研究取得良好结果后，其中几种改良Hb溶液目前正在进行III期临床试验。其中，双阿司匹林交联血红蛋白（DCLHb）已用于心脏和骨科手术以及交通事故受害者的复苏。多中心试验的初步结果目前正在分析中。
