Pharmacodynamic study of polyethylene glycol conjugated bovine hemoglobin (PEG-bHb) in rats.
The purpose of this study was to determine the pharmacodynamics of polyethylene glycol (PEG) conjugation on stroma-free bovine hemoglobin, hemorrhage shock, and exchange transfusion rat models were used. In both rat models, blood pressure increased in 6% PEG-bHb treated animals was significantly higher than dextran 70, even than whole blood (isovolume of hemorrhage) transfusion. Six percent PEG-BHb could ameliorate the micro-circulation of the experimental animals markedly, including reducing the blood viscosity and improving the blood flow. This effect of PEG-bHb was superior to autogenous blood which only recovered 50% blood flow, and there's no effect on blood flow when used isovolumic dextran 70. Tissue oxygenations of rats were evaluated by the oxygen dependent quenching of phosphorescence using an Oxyspot phosphorimeter, and the results showed that capability of oxygen-delivery of PEG-bHb was close to autogenous blood and superior to dextran 70. Based on these effects, the survival rates of animals treated with PEG-bHb were close to that of the whole blood transfusion. And data suggested that half of the hemorrhage transfusion is the reasonable therapeutic dosage. In conclusion, PEG-bHb is an effective blood substitute with powerful tissue oxygenation and blood volume expansion.
Beijing Kaizheng Biotech Developing Ltd., Beijing, PR China.
Zhigang
Z
Bi
Xueying
X
He
Xiaowei
X
Zhang
Yong
Y
Jiang
Kesen
K
Zhao
Qian
Q
Liu
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000494:pharmacology* / Q000627:therapeutic use; D001809:Blood Viscosity / Q000187:drug effects; D002417:Cattle; D002712:Chlorides / Q000097:blood; D005078:Exchange Transfusion, Whole Blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology* / Q000627:therapeutic use; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D009132:Muscles / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000628:therapy; D014699:Venules / Q000187:drug effects
D001802:Blood Substitutes; D002712:Chlorides; D006454:Hemoglobins; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols