Effect of BW12C on oxygen affinity of haemoglobin in sickle-cell disease.
Eight subjects with sickle-cell disease in the symptom-free steady-state received a single one-hour infusion of the new anti-sickling agent BW12C on a total of eleven occasions. A dose-dependent increase in wholeblood oxygen affinity was observed, resulting from the action of BW12C in stabilising the oxy-conformation of haemoglobin and causing a left shift of the oxygen saturation curve. At the highest dose given (20 mg/kg bodyweight), up to 23% of haemoglobin was modified to a BW12C-reacted high-affinity form without evidence of tissue hypoxia. There was biochemical and rheological evidence for a transient decrease in haemolytic rate.
Keidan
A J
AJ
Franklin
I M
IM
White
R D
RD
Joy
M
M
Huehns
E R
ER
Stuart
J
J
D000328:Adult; D000447:Aldehydes / Q000008:administration & dosage / Q000494:pharmacology*; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000188:drug therapy; D001219:Aspartate Aminotransferases / Q000032:analysis; D001547:Benzaldehydes; D001663:Bilirubin / Q000032:analysis; D001667:Binding, Competitive; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004906:Erythrocyte Count; D004907:Erythrocyte Deformability / Q000187:drug effects; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007263:Infusions, Parenteral; D007958:Leukocyte Count; D008297:Male; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D010108:Oxyhemoglobins / Q000032:analysis; D013789:Thalassemia / Q000097:blood / Q000188:drug therapy; D013997:Time Factors
D000447:Aldehydes; D001547:Benzaldehydes; D006451:Hemoglobin, Sickle; D010108:Oxyhemoglobins; C039599:5-(2-formyl-3-hydroxyphenoxy)pentanoic acid; D001219:Aspartate Aminotransferases; D001663:Bilirubin; D010100:Oxygen