The ability of polyethylene glycol conjugated bovine hemoglobin (PEG-Hb) to adequately deliver oxygen in both exchange transfusion and top-loaded rat models.
The purpose of this study was to determine whether a six gram percent (g%) solution of the hemoglobin based oxygen carrier, polyethylene glycol conjugated bovine hemoglobin (PEG-Hb) could adequately deliver oxygen in both partial exchange transfusion and top-loaded rat models. This study measured tissue oxygen tension, circulatory retention and cardiovascular effects following both 30% exchange transfusion and 20 to 25 mL/kg top-loaded infusions of PEG-Hb. Oxygen delivery to rat tissues was determined using an oxygen dependent phosphorescence quenching method (Oxyspot). Telemetric intravascular blood pressure probes monitored heart rate and mean arterial pressure. In both models, six g% PEG-Hb (P50-15 torr) was shown to oxygenate tissue better than stroma-free bovine Hb (P50-26 torr), cross-linked bovine Hb (P50-48 torr) or simple plasma expanders. The mean circulatory half life of PEG-Hb was 15.0 +/- 2.3 hours and 17.4 +/- 1.6 hours for exchange transfusion and 25 mL/kg top-loaded rat models, respectively. Mean arterial pressure (MAP) in PEG-Hb treated rats was insignificantly different from sham controls undergoing a 30% exchange transfusion or following a top-loaded infusion. In conclusion, the PEG conjugated form of bovine Hb with its relatively long vascular persistence may possess characteristics that facilitate tissue oxygenation in the rat.
Conover
C D
CD
Research and Development, Formulations-Toxicology Department, Enzon Inc., Piscataway, NJ 08854, USA.
Linberg
R
R
Shum
K L
KL
Shorr
R G
RG
D000818:Animals; D001794:Blood Pressure; D001802:Blood Substitutes / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D002417:Cattle; D005260:Female; D006339:Heart Rate; D006454:Hemoglobins / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism
D001802:Blood Substitutes; D006454:Hemoglobins; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols; D010100:Oxygen