Towards a novel haemoglobin-based oxygen carrier: Euro-PEG-Hb, physico-chemical properties, vasoactivity and renal filtration.
Blood transfusion is still a critical therapy in many diseases, traumatic events and war battlefields. However, blood cross-matching and storage may limit its applicability, especially in Third World countries. Moreover, haemoglobin, which in red blood cells is the key player in the oxygen transport from lung to tissues, when free in the plasma causes hypertension and renal failure. This investigation was aimed at the development of a novel haemoglobin-based oxygen carrier with low vasoactivity and renal filtration properties. Human haemoglobin was chemically conjugated with polyethylene glycol (PEG) under either aerobic or anaerobic conditions, following different chemical procedures. The resulting PEGylated haemoglobin products were characterized in terms of oxygen affinity, cooperativity, effects of protons and carbon dioxide concentration, and oxidation stability, and were transfused into rats to evaluate vasoactivity and renal filtration. A deoxyhaemoglobin, conjugated with seven PEG and seven propionyl groups, which we called Euro-PEG-Hb, did not produce profound hypertension, was 99% retained within 6 h, and exhibited oxygen binding properties and allosteric effects more similar to human haemoglobin A than the other tested PEGylated haemoglobin derivatives, thus appearing a very promising candidate as blood substitute.
Portöro
I
I
Institute of Human Physiology and Clinical Experimental Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Kocsis
L
L
Hermán
P
P
Caccia
D
D
Perrella
M
M
Ronda
L
L
Bruno
S
S
Bettati
S
S
Micalella
C
C
Mozzarelli
A
A
Varga
A
A
Vas
M
M
Lowe
K C
KC
Eke
A
A
D000332:Aerobiosis; D000693:Anaerobiosis; D001802:Blood Substitutes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001803:Blood Transfusion; D003906:Developing Countries; D005374:Filtration; D006454:Hemoglobins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007552:Isotonic Solutions / Q000737:chemistry / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology*; D007700:Kinetics; D008958:Models, Molecular; D010100:Oxygen / Q000097:blood; D010108:Oxyhemoglobins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011485:Protein Binding; D011487:Protein Conformation
D001802:Blood Substitutes; D006454:Hemoglobins; D007552:Isotonic Solutions; D010108:Oxyhemoglobins; D011092:Polyethylene Glycols; D010100:Oxygen