Evaluation of a Pyridoxalated-Hemoglobin-Polyoxyethylene Conjugate (PHP) as an Oxygen Carrying Plasma Expander in Lethal Anemia

PHP, mean molecular weight of approximately 90,000 daltons, is produced by chemical modifications of outdated human red cell hemoglobin (Hb). The P50 value of PHP is 22 ± 0.7mmHg. Eleven healthy mongrel dogs were exposed to severe anemia to a hematocrit of 5 ± 2% by normovolemic exchange (ET) with PHP (n=5) or a plasma expander, Hespan (Control, n=6). Hb concentration in the preparation is 6.0 g/dl. All the animals with PHP tolerated the procedure well and have survived for 1 year at sacrifice while five of the controls died within a week (p=0.004). Reductions in hematological and coagulation parameters occurred following ET and these parameters returned to the normal ranges by 4 weeks post ET. Renal function parameters (serum urea and creatinine) remained in the normal range throughout the experimental period. A transient slight increase in the hepatic enzyme SGOT was observed. Open biopsies of major organs at 2 weeks post ET showed vacuolated cells in the liver and kidneys. Normal histology was noted at and after 3 months. Oxygen transport properties as examined by arterial-venous oxygen differences, oxygen delivery and oxygen extraction showed that PHP continued to transport oxygen up to 48 hours studied post ET. PHP functioned as effectively as red blood cells at 6 hours in oxygen delivery to the tissues. PHP effectively supported life at lethal levels of anemia and is physiologically well accepted.