Evaluation of the oxygen delivery ability of PEG-hemoglobin in Sprague-Dawley rats during hemodilution.
Polyethylene glycol (PEG) conjugation allows bovine hemoglobin (Hb) to retain its oxygen delivery capability while increasing its plasma expansion capacity. To determine whether PEG-Hb's ability to sustain life is due to its oxygen delivery capability rather than its plasma expansion capacity, Sprague-Dawley rats were exchange-transfused up to an 85% hematocrit reduction with either PEG-Hb, PEG-50%-methemoglobin (PEG-mHb), PEG-carbon monoxide hemoglobin (PEG-COHb) or PEG-human serum albumin (PEG-HSA). Survival and respiratory rates were monitored during the exchange transfusion, at five minutes, 24 hours and 48 hours post operative. Rats surviving 14 days were evaluated for hematology, blood chemistry and histopathology. Rats infused with PEG-Hb had a survival rate of 100% during the transfusion and 79% at 24 hours, as compared to 24 hour survival rates of 30% for PEG-mHb, and 0% for both PEG-COHb and PEG-HSA. PEG-Hb treated rats that survived the 2 week observation period had normal hematological and blood chemistry levels and no significant morphological effects. Therefore, this study demonstrates that PEG-Hb can sustain life while similar plasma expansion agents with less oxygen delivery capability are not as effective.
Conover
C
C
Formulations-Toxicology Department, Enzon Inc., Piscataway, NJ 08854, USA.
Linberg
R
R
Lejeune
L
L
Gilbert
C
C
Shum
K
K
Shorr
R G
RG
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D001831:Body Temperature; D002417:Cattle; D006400:Hematocrit; D006438:Hemodilution / Q000379:methods*; D006454:Hemoglobins / Q000494:pharmacology*; D008297:Male; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001802:Blood Substitutes; D006454:Hemoglobins; D010108:Oxyhemoglobins; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols; D010100:Oxygen