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A Blood SuBStitute
The quest for a substitute for precious blood — always in
short supply — was also under way. Supplying oxygen is just
one of blood’s many vital functions, but for short-term blood
replacement (which could save lives in emergencies) oxygen-
carrying capacity is the primary concern. PFCs have been
considered for that purpose since the early 1960s. At atmospheric
pressure and body temperature, PFCs dissolve large amounts
of gases — oxygen and carbon dioxide in particular. Unlike the
binding and release of oxygen from hemoglobin in the blood,
the dissolution of oxygen in PFCs is entirely passive. When PFC
emulsions are administered intravenously, they are loaded with
oxygen in the lungs, where the oxygen pressure is high, and
release oxygen in tissues where the oxygen tension is low. It is
this characteristic of PFCs that is the subject of ongoing research.
A therApy for dCS
Because of their high nitrogen-carrying capacity it was not
long until PFCs caught the attention of diving and hyperbaric
physiologists. In the 1980s it was shown that small animals
can survive otherwise fatal decompressions if they receive an
intravenous emulsion of PFCs immediately after decompressing.
Progress in this area proved to be slower than expected, but our
knowledge and technologies continue to improve. A definitive
answer has not yet been found, but research is ongoing.
How have PFCs been used in medicine?
Steven Hill:
PFCs were approved several years ago as oxygen
carriers for use as a temporary measure during ischemia in
coronary angioplasty procedures. The procedure got so efficient,
however, PFCs became unnecessary for angioplasty and stents.
The procedure progressed to the point PFCs weren’t needed.
In the late 1990s or early 2000s PFCs advanced into late-
stage clinical trials that investigated their ability to enhance
hemodilution. Hemodilution is a method of preserving
hemoglobin mass during high-blood-loss surgical procedures
in people who refuse blood transfusions. PFCs were used to
enhance the oxygen-delivery capability of and the amount of
dissolved oxygen in the fluid phase of the blood during surgery,
which allowed doctors to preserve more of patients’ own red
cells for postsurgical readministration. The late-phase trial
called for these patients to be significantly hemodiluted, but
we ran into problems with the loss of other elements of blood
such as viscosity and clotting factors. There was no problem
with oxygenation or oxygen delivery — the PFCs did what they
were supposed to do. But the patients became hypotensive
and required clotting factors and platelets at the end of the
procedure because they developed acquired coagulopathies.
It’s important to think of PFCs as a temporizing measure.
You can’t give PFCs over a long period because the body needs
time to get rid of them. Breakdown products of the PFCs build
up in the system because the body can’t excrete them fast
enough, and that causes problems. You can’t keep somebody
alive for months with just PFCs in their bloodstream.
What future medical uses of PFCs do you envision??
Hill:
PFCs are effective in situations where you need short-
term oxygen delivery without red blood cells. I don’t know
if the military has looked at PFCs for use in trauma, but the
compounds might be suitable for administration out in the field
to enhance oxygen delivery during the evacuation to the hospital.
In cases of organs with transient ischemia (impaired or
interrupted blood flow), PFCs might be able to get past the
stricture because of the small size of PFC molecules relative
to red blood cells. The PFCs could conduct oxygen delivery
past a blocked artery until the vessel opened up again. In a
patient with serious transient ischemic attacks (TIAs), for
example, PFCs could preserve oxygenation of brain tissue.
Doctors are starting to use angioplasty in the carotid artery
and the artery inside the brain to try to open those. Perhaps
potential strokes could be delayed or reduced in severity until
those vessels could be reopened. A dose of PFCs administered
to a patient with a pending stroke could increase oxygen
delivery past the stenosed vessel and conceivably decrease the
size of the stroke or reverse it altogether.
Bruce Spiess:
Air embolism is nearly universal in heart surgery,
and research with PFCs in the 1980s and ’90s showed up to a 98
percent reduction in bubble load. In war fighting, sudden death
from improvised explosive devices (IEDs) is caused by rupture of
alveoli (air sacs in the lungs) and subsequent air emboli leading
to air bubbles in the heart and/or brain. This is analogous to
pulmonary barotrauma in divers. Although death is often so
sudden there is not time to administer PFCs before cardiac arrest,
we believe PFCs could still be very useful in these circumstances.
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M I CH A E L J UNG / S HU T T E R S T OC K