Biochemistry - Prolonged Preservation of the Heart Prior to Transplantation

Picture this. A man is involved in a severe car crash in
Florida which has left him brain-dead with no hope for any
kind of recovery. The majority of his vital organs are
still functional and the man has designated that his organs
be donated to a needy person upon his untimely death.
Meanwhile, upon checking with the donor registry board, it
is discovered that the best match for receiving the heart of
the Florida man is a male in Oregon who is in desperate need
of a heart transplant. Without the transplant, the man will
most certainly die within 48 hours. The second man’s
tissues match up perfectly with the brain-dead man’s in
Florida. This seems like an excellent opportunity for a
heart transplant. However, a transplant is currently not a
viable option for the Oregon man since he is separated by
such a vast geographic distance from the organ. Scientists
and doctors are currently only able to keep a donor heart
viable for four hours before the tissues become irreversibly
damaged. Because of this preservation restriction, the
donor heart is ultimately given to someone whose tissues do
not match up as well, so there is a greatly increased chance
for rejection of the organ by the recipient. As far as the
man in Oregon goes, he will probably not receive a donor
heart before his own expires.

Currently, when a heart is being prepared for
transplantation, it is simply submerged in an isotonic
saline ice bath in an attempt to stop all metabolic activity
of that heart. This cold submersion technique is adequate
for only four hours. However, if the heart is perfused with
the proper media, it can remain viable for up to 24 hours.
The technique of perfusion is based on intrinsically simple
principles. What occurs is a physician carefully excises
the heart from the donor. He then accurately trims the
vessels of the heart so they can be easily attached to the
perfusion apparatus. After trimming, a cannula is inserted
into the superior vena cava. Through this cannula, the
preservation media can be pumped in.

What if this scenario were different? What if doctors were
able to preserve the donor heart and keep it viable outside
the body for up to 24 hours instead of only four hours? If
this were possible, the heart in Florida could have been
transported across the country to Oregon where the perfect
recipient waited. The biochemical composition of the
preservation media for hearts during the transplant delay is
drastically important for prolonging the viability of the
organ. If a media can be developed that could preserve the
heart for longer periods of time, many lives could be saved
as a result.

Another benefit of this increase in time is that it would
allow doctors the time to better prepare themselves for the
lengthy operation. The accidents that render people
brain-dead often occur at night or in the early morning.
Presently, as soon as a donor organ becomes available,
doctors must immediately go to work at transplanting it.
This extremely intricate and intense operation takes a long
time to complete. If the transplanting doctor is exhausted
from working a long day, the increase in duration would
allow him enough time to get some much needed rest so he can
perform the operation under the best possible circumstances.

Experiments have been conducted that studied the effects of
preserving excised hearts by adding several compounds to the
media in which the organ is being stored. The most
successful of these compounds are pyruvate and a pyruvate
containing compound known as
perfluoroperhydrophenanthrene-egg yolk phospholipid
(APE-LM). It was determined that adding pyruvate to the
media improved postpreservation cardiac function while
adding glucose had little or no effect. To test the
function of these two intermediates, rabbit hearts were
excised and preserved for an average of 24.5 1 0.2 hours on
a preservation apparatus before they were transplanted back
into a recipient rabbit. While attached to the preservation
apparatus, samples of the media output of the heart were
taken every 2 hours and were assayed for their content. If
the compound in the media showed up in large amounts in the
assay, it could be concluded that the