Effects of partial and total isovolemic exchange transfusion in fully conscious rats using pyridoxylated...

Stroma-free hemoglobin (SFHb) treated with pyridoxal 5'-phosphate (PP) was intermolecularly cross-linked with glutaraldehyde to give pyridoxylated polyhemoglobin (PP-PolyHb) solution (14.0 g/dl) with colloid osmotic pressure = 25 torr and a P50 = 20 torr. To evaluate PP-PolyHb as a blood substitute, fully conscious rats with chronic cannulations were subjected to blood replacement (30-100%) by a new continuous isovolemic exchange transfusion set up. Crystalline SFHb, PP-SFHb, PP-PolyHb, bovine serum albumin (BSA) and Ringer's solution were tested. Respiration, pulse and arterial blood pressure were more stable following transfusion with PP-PolyHb or PP-SFHb compared to BSA. By 7-8 days post-exchange, hematological changes returned to normal. Plasma retention of PP-PolyHb was 10-15 times longer than either crystalline SFHb or PP-SFHb for major blood exchanges. A T1/2 of 30 h was obtained for PP-PolyHb after total replacement. Long-term survival rates of 80, 63 and 50%, following replacement of 70, 85 and 100%, respectively, were significantly higher (p less than 0.05) than survival obtained for all other solutions tested. Superiority of PP-PolyHb over other fluids was clearly demonstrated.