Monograph: |
Haemoglobin
Haemoglobin has the property of reversible oxygenation and
is the respiratory pigment of blood. Solutions of haemoglobin
or modified haemoglobin have been investigated as blood
substitutes.
The structure of haemoglobin gives a non-linear oxygen dis-
sociation curve: almost maximum oxygen saturation occurs
in normal arterial blood without the need for oxygen-enriched
air. Thus the use of haemoglobin solutions for emergency use
appears logical. Initial animal experiments with haemoglobin
from haemolysed erythrocytes resulted in serious renal dam-
age but haemoglobin is not itself nephrotoxic and the devel-
opment of stroma-free haemoglobin solutions reduced this
toxicity. However, once released from the erythrocytes. hae-
moglobin loses its ability to hold 2,3-diphosphoglycerate.
which is essential for the delivery of oxygen, and haemoglob-
in, being a small molecule, is rapidly excreted by the kidneys.
Various methods have been tried to overcome these problems:
addition of pyridoxine 5-phosphate and formation of
cross linked haemoglobin restore the oxygen affinity to that of
whole blood and polymerisation or micro encapsulation in a
lipid membrane extend the half-life. Polymerisation has the
added advantages that this process is virucidal and also low-
ers the osmolality of the solution permitting higher concentra-
tions to be used. There are. however, reservations concerning
haemoglobin solutions as blood substitutes: blood itself must
be available for their production, although expired blood may
be employed and there is also concern about impairment of
immune mechanisms. The recent production of recombinant
human haemoglobin may overcome these problems.
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