Yabuki A, Matsushita M, Malchesky P S, Iwasaki K, Iwashita Y, Nosé Y
Department of Artificial Organs, Cleveland Clinic Foundation.
ASAIO Trans. 1988 Jul-Sep;34(3):773-7.
In sickle cell disease (SCD) microcirculatory blockage by red blood cells (RBC) occurs because of their low oxygen concentration, which results in both sickling and painful crises. Pyridoxalated hemoglobin polyoxyethylene (PHP), developed from human RBC hemoglobin (Hb) by chemical modification as an oxygen carrier, was evaluated in vitro for its ability to reverse cell sickling. PHP solutions of 6 or 8 g % Hb and a P50 of 20 mmHg were evaluated. RBC were obtained from SCD patients treated by exchange transfusion. The in vitro positive pressure filtration method (47 mm 5 microns Nuclepore membrane) was used. Comparisons of PHP with low oxygen carrier solutions (Hespan, saline) were made at flows of 0.43 to 6.0 ml/min. PO2 increases in a 20% mixture of air saturated solutions with deoxygenated sickle cell suspensions (SCS), at a hematocrit of 1%, were significantly higher in PHP as compared with saline and Hespan. The filtration resistance of deoxygenated SCS mixed with PHP was significantly lower than that of deoxygenated SCS mixed with saline and Hespan, and was comparable to that of air oxygenated SCS. By the 20% (v/v) addition of air saturated PHP to deoxygenated SCS, 89 +/- 2% of the sickled cells were unsickled. A novel artificial capillary system (ACS) modeling the dynamics of the microcirculation of the body was used. With the ACS plugged with deoxygenated cells, perfusion with oxygenated cell-PHP solutions was significantly more efficient in reversing the blockage than oxygenated saline and Hespan solutions. PHP reverses cell sickling by its effective delivery of oxygen.
在镰状细胞病（SCD）中，红细胞（RBC）会因氧浓度低而发生微循环阻塞，这会导致镰变和疼痛危象。吡哆醛化血红蛋白聚氧乙烯（PHP）是通过化学修饰从人RBC血红蛋白（Hb）开发而来的一种氧载体，其在体外逆转细胞镰变的能力得到了评估。评估了6或8 g% Hb且P50为20 mmHg的PHP溶液。RBC取自接受换血治疗的SCD患者。采用体外正压过滤法（47 mm 5微米核孔膜）。在0.43至6.0 ml/min的流速下，将PHP与低氧载体溶液（贺斯、生理盐水）进行了比较。在血细胞比容为1%的情况下，与生理盐水和贺斯相比，在含脱氧镰状细胞悬液（SCS）的20%空气饱和溶液混合物中，PHP组的PO2升高显著更高。与脱氧SCS与生理盐水和贺斯混合相比，脱氧SCS与PHP混合的过滤阻力显著更低，与空气氧合SCS相当。通过向脱氧SCS中添加20%（v/v）空气饱和的PHP，89±2%的镰状细胞不再镰变。使用了一种模拟人体微循环动态的新型人工毛细血管系统（ACS）。当ACS被脱氧细胞堵塞时，用氧合细胞-PHP溶液灌注在逆转阻塞方面比氧合生理盐水和贺斯溶液显著更有效。PHP通过有效输送氧气来逆转细胞镰变。
