In vivo evaluation of pyridoxalated-polymerized hemoglobin solution

Previous evaluations of stroma free hemoglobin solutions (SFHS) revealed two problems, a low P50 (13 to 15 torr) which theoretically limits oxygen off-loading to tissues, and a short intravascular half time of only 3.5 hours. To correct these problems the hemoglobin molecule was pyridoxalated and polymerized to raise the P50 (20 to 22 torr) and to increase the plasma half-disappearance time to 25 hours. In the current investigation, rats exchange transfused to 75 per cent of their initial blood volume with SFHS exhibited centrilobular liver necrosis 12 and 24 hours after the transfusion as a result of the hypovolemic state induced by the hemoglobin diuresis. In contrast, animals administered pyridoxalated polymerized hemoglobin solution (Pr-Pl-Hb) displayed a normal hepatic morphologic finding. Renal morphologic findings in the two groups were similar except for the smaller quantities of hemoglobin observed in the proximal and distal tubules of Pr-Pl-Hb animals. This finding may be a result of the slower degradation of Pr-Pl-Hb in the intravascular compartment. Renal function in Pr-Pl-Hb remained normal after exchange transfusion, while the BUN in SFHS treated animals increased significantly due to the state of dehydration. Thus, Pr-P1-Hb represents an improvement over the previously tested SFHS in both P50 and intravascular half-time and, because of lowered osmotic and oncotic activities, it may be used in higher concentration to improve oxygen carrying capacity.