Artificial Red Cells : Physiological Importance of the Ligand Reaction Dynamism and the New Application for Ligand Therapy

化学修饰血红蛋白（Hb）溶液作为人工O_2载体表现出血管收缩和高血压，可能是由于内源性NO和CO作为血管松弛因子的高亲和力，以及由于更快的O_2释放诱导自调节性血管收缩。另一方面，细胞型乙型肝炎囊泡（HbV）不会引起这种副作用。本文通过物理化学技术分析了配体气体分子的反应，发现HbV的反应速度要慢得多，这是由于高浓度Hb溶液在细胞内形成气体扩散屏障，以及HbV在窄管中流动时，其横向扩散受到阻碍。此外，我们测试了HbV作为外源性CO载体，因为内源性CO具有细胞保护作用。在引起失血性休克后，用co结合HbV对大鼠进行复苏。在再灌注时表现出细胞保护作用，CO迅速解离，经肺呼出。未发现与一氧化碳毒性相关的症状。这一结果暗示了人造红细胞作为一种新的配体疗法的可能性。

Chemically modified hemoglobin (Hb) solutions as artificial O_2 carriers show vasoconstriction and hypertension presumably due to the high affinity for endogenous NO and CO as vasorelaxation factors, and due to the faster O_2-release that induces autoregulatory vasoconstriction. On the other hand, cellular-type Hb-vesicle (HbV) does not induce such side effects. Herein we analyzed the reactions of ligand gaseous molecules by physicochemical techniques, and found out that HbV shows much slower reactions and it is due to the intracellular gas diffusion barrier induced by a concentrated Hb solution, and the retarded lateral diffusion of HbV when it flows in a narrow tube. In addition, we tested HbV as an exogenous CO carrier because endogenous CO is cytoprotective. After inducing hemorrhagic shock, rats were resuscitated with CO-bound HbV. It showed cytoprotective effect at reperfusion, and CO was dissociated rapidly and exhaled through the lung. No symptom related to toxicity of CO was detected. The results imply the possibility of artificial red cells for a new ligand therapy.