Artificial blood

The invention:

Aperfluorocarbon emulsion that serves as a blood
plasma substitute in the treatment of human patients.

The person behind the invention:

Ryoichi Naito (1906-1982), a Japanese physician.



Blood Substitutes

The use of blood and blood products in humans is a very complicated
issue. Substances present in blood serve no specific purpose
and can be dangerous or deadly, especially when blood or blood
products are taken from one person and given to another. This fact,
combined with the necessity for long-term blood storage, a shortage
of donors, and some patients’ refusal to use blood for religious reasons,
brought about an intense search for a universal bloodlike substance.
The life-sustaining properties of blood (for example, oxygen transport)
can be entirely replaced by a synthetic mixture of known chemicals.
Fluorocarbons are compounds that consist of molecules containing
only fluorine and carbon atoms. These compounds are interesting
to physiologists because they are chemically and pharmacologically
inert and because they dissolve oxygen and other gases.
Studies of fluorocarbons as blood substitutes began in 1966,
when it was shown that a mouse breathing a fluorocarbon liquid
treated with oxygen could survive. Subsequent research involved
the use of fluorocarbons to play the role of red blood cells in transporting
oxygen. Encouraging results led to the total replacement of
blood in a rat, and the success of this experiment led in turn to trials
in other mammals, culminating in 1979 with the use of fluorocarbons
in humans.


Clinical Studies

The chemical selected for the clinical studies was Fluosol-DA,
produced by the Japanese Green Cross Corporation. Fluosol-DA
consists of a 20 percent emulsion of two perfluorocarbons (perfluorodecalin
and perfluorotripopylamine), emulsifiers, and salts
that are included to give the chemical some of the properties of
blood plasma. Fluosol-DA had been tested in monkeys, and it had
shown a rapid reversible uptake and release of oxygen, a reasonably
rapid excretion, no carcinogenicity or irreversible changes in the animals’
systems, and the recovery of blood components to normal
ranges within three weeks of administration.
The clinical studies were divided into three phases. The first
phase consisted of the administration of Fluosol-DA to normal human
volunteers. Twelve healthy volunteers were administered the
chemical, and the emulsion’s effects on blood pressure and composition
and on heart, liver, and kidney functions were monitored. No
adverse effects were found in any case. The first phase ended in
March, 1979, and based on its positive results, the second and third
phases were begun in April, 1979.
Twenty-four Japanese medical institutions were involved in the
next two phases. The reasons for the use of Fluosol-DA instead of
blood in the patients involved were various, and they included refusal
of transfusion for religious reasons, lack of compatible blood,
“bloodless” surgery for protection from risk of hepatitis, and treatment
of carbon monoxide intoxication.
Among the effects noticed by the patients were the following: a
small increase in blood pressure, with no corresponding effects on
respiration and body temperature; an increase in blood oxygen content;
bodily elimination of half the chemical within six to nineteen
hours, depending on the initial dose administered; no change in
red-cell count or hemoglobin content of blood; no change in wholeblood
coagulation time; and no significant blood-chemistry changes.
These results made the clinical trials a success and opened the door
for other, more extensive ones.


IMPACT

Perfluorocarbon emulsions were initially proposed as oxygencarrying
resuscitation fluids, or blood substitutes, and the results of
the pioneering studies show their success as such. Their success in
this area, however, led to advanced studies and expanded use of these compounds in many areas of clinical medicine and biomedical
research.
Perfluorocarbon emulsions are useful in cancer therapy, because
they increase the oxygenation of tumor cells and therefore sensitize
them to the effects of radiation or chemotherapy. Perfluorocarbons
can also be used as “contrasting agents” to facilitate magnetic resonance
imaging studies of various tissues; for example, the uptake of
particles of the emulsion by the cells of malignant tissues makes it
possible to locate tumors. Perfluorocarbons also have a high nitrogen
solubility and therefore can be used to alleviate the potentially
fatal effects of decompression sickness by “mopping up” nitrogen
gas bubbles from the circulation system. They can also be used to
preserve isolated organs and amputated extremities until they can
be reimplanted or reattached. In addition, the emulsions are used in
cell cultures to regulate gas supply and to improve cell growth and
productivity.
The biomedical applications of perfluorocarbon emulsions are
multidisciplinary, involving areas as diverse as tissue imaging, organ
preservation, cancer therapy, and cell culture. The successful
clinical trials opened the door for new applications of these
compounds, which rank among the most versatile compounds exploited
by humankind.