What are blood substitutes?
Blood substitutes are
chemical compounds designed to transport the oxygen and to replace the
whole blood or RBC in transfusion.This compounds represent an attractive
alternative for blood transfusion and a way of rezolving the associated
riscs (transmisible desises, allergic reactions, s. o.).
In animals, associated riscs of blood transfusion are
represented by acute haemolisis, infections caused by contaminated blood,
parasitic disease (Haemobartonella, Anaplasma, Babesia) and
viral disease (feline or bovine leukemia, equine infectious anaemia)
transmision, hipocalcemia caused by citrate excess and hipervolemia.
The blood substitutes eliminates this riscs by the fact
that they are universal use chemical compounds, nonantigenic and chemicaly
inert. The ideal blood substitute must be:
- capable of
re-filling quickly the vascularity and suply oxygen to the tissues;
- without antigenity;
- incapable to transmit infections;
- nontoxic;
- without secundary reactions;
- efficient in deliverring the oxygen;
- of universal use;
- with half life time of at least a few days.
The
present compounds ensures the efficient oxigen delivery to tissues,
have a half life time big enough and the allergic reactions determined
are minimum.
The role of present blood substitutes is to replace
the oxygen transport function of hemoglobin. In the same time, this
oxygen carriers are also volume expandants, by the contained electrolitic
solution.
There are two types of chemical compounds used as base
for blood substitutes:
a)
Hemoglobin, the natural vector of oxygen.
The free hemoglobin may be
used as oxygen vector, but non- protected by the eritrocyte membrane
it dissociates into dimers and monomers which, having reduced dimmensions
(16 kDa and 32 kDa), extravasates easily and are rapidly eliminated.
The free haemoglobin solution may contain remains of eritrocyte membranes
which, in a alien body, can produce severe alergic reactions. From
this matter, hemoglobin used as blood substitute must undergo purification
and chemical modification procedures for stabilizing the molecule
in a shape that allows oxygen to be readily eliberated and in the
same time to show a long half life time.
b) Perfluorocarbons,
inert chemical compounds and very good solvents for gases.
Perfluorocarbons are synthetic chemical compounds with aromatic or
alifatic structure which have the hydrogene atoms substituted with
fluor atoms, chemicaly inert and insoluble in water and lipids. Their
insolubility makes the blood substitutes based on perfluorocarbons
to be presented as an emulsion.
Steps in developping the blood
substitutes:
1934:
The first oxygen vector researched was the free haemoglobin. In 1934,
Amberson, after he made some experiments with lised red blood cells
administrated in partialy exangvinated cats, he defined the role of
hemoglobin and demonstrated that free haemoglobin can be used as oxygen
carrier. However, the experiments made with free hemoglobin showed a
few major desadvantages in its use as oxygen carrier. This desadvanteges
are:
- alergic reactions;
- extravazation and quick elimination;
- hypertensive effect;
- and inefficiency in oxygen delivery.
The
following experiments elucidated the causes of this secundary reactions
and had could be eliminated by alterrings done to the hemoglobin. This
experiments were decisive in the new artificial blood.
1957:
In the same time, obtaining artifficial cels has oppened a new horisont.
In 1957, Chang and coworkers have obtained the first artificial cells
as artificial red blood cells. Artificial red blood cells obtained by
him were made from spheric polimeric membranes, with micro-drops of
haemoglobin and red blood cells enzymes inside. The artificial cells
creates the premise of obtainning oxygen vectors with a content closer
to the one of bylogical red blood cells, wich can be immproved.
1966:
A new discovery are perfluorocarbons. In 1966 Clark noticed that perfluorocarbons
are excellent solvents for gases, in special for oxygen and carbon dioxide.
A year later, Clark and Gollan showed that mices can survive completly
imersed in oxygenated fluorocarbons or in oxygenated silicon oil. Those
discoveryes leaded to research of perfluorocarbons as hemoglobin substitute
and its possible uses as breathing liquides in sea's high depths divings.
Blood
substitutes based on perfluorocarbons are still intensive researched
and are attractive due to the next advantages:
- are chemical
inert and hard to decompose, so they have the highest half life
time;
- the obtainning costs are lower than in the case of haemoglobin
and a byologic source of haemoglobin is not necessary;
- being sintetic compounds, the risc of transmiting diseses is considerable
lower;
- they are not metabolised in the body, being eliminated by pulmonary
way.
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