Comparison of PEG-modified albumin and hemoglobin in extreme hemodilution in the rat

We have reported a new polyethylene glycol (PEG)-modified, hemoglobin-based O-2 carrier (MP4) with novel properties, including a large molecular excluded volume and low Po-2 necessary to obtain 50% O-2 (similar to6 Torr). To evaluate the ability of MP4 to transport O-2, we compared it with PEG-modified albumin (MPA) using the identical chemistry of attachment of PEG chains. The resulting solutions were well matched with respect to all physical properties except that MP4 is an O carrier, whereas MPA is not. An additional solution, 10% pentastarch, was matched with the PEG-modified proteins with regard to oncotic activity and viscosity but does not contain PEG. The model used to evaluate O transport was continuous exchange transfusion in the rat until the hematocrit was virtually unmeasureable. Objective end points included survival and the onset of anaerobic metabolism, signaled by acid-base derangement and accumulation of lactic acid. Continuous exchange transfusion of 2.5 blood volumes in rats (n = 5 in each treatment group) was carried out over 60 min, such that the final hematocrit was between 0 and 5% in all animals. Animals were observed for an additional 70 min, when survivors were killed. Overall survival for the MP4 animals was 100%; no animal that received either pentastarch or MPA survived. The hematocrit at which tactic acid began to rise was similar to 14.8% in both pentastarch and MPA animals and 7.4% in the animals that received MP4. In all groups, the total hemoglobin was similar to5 g/dl at this point. We conclude that, despite its low Po-2 necessary to obtain 50% 0,, MP4 effectively substitutes for red blood cell hemoglobin in its ability to oxygenate tissues in extreme hemodilution.