X-Message-Number: 2909
Date: 18 Jul 94 10:53:53 EDT
From: "Steven B. Harris" <>
Subject: CRYONICS.Perfusion Tradeoffs

Dear Cryonet:

    In response to Robert Cardwell, the potential problems with
doing less than 4 vessel brain perfusions are as I indicated, and
the 4-vessel aorta-based cryoprotectant perfusion of the brain
should be considered state-of-the-art.  Thus, if you are a
cryonics organization offering services to the public, there is
little excuse for offering anything less in your main lab if you
advertise yourself as being state-of-the-art.  A good cryonics
organization will end up doing at least some fraction of its
suspensions this way.

    But what about the emergencies and one or two day delays
between cardiac arrest and cryoprotectant perfusion which will
always occur to even the best organizations occasionally (and
which will occur regularly to some organizations?).  What about
clients who are stuck in cardiac arrest out of the country on a
weekend, or who have experienced for one reason or another so
much warm ischemia that any further warm-time carries the real
possibility of not being able to perfuse the brain at all?  What
is the best choice if you have to choose between a 2-vessel
perfusion of the brain with a portable pump followed by a dry ice
freeze before shipping, *versus* 3 extra days at water ice temps
followed by a fancy 4-vessel perfusion and more careful decent to
dry ice temps?  How do you judge the tradeoffs?

   I wish I knew.  Research will tell some of the answers, but
not all of them.  One problem is that human brain perfusion
anatomy is not at all like that of any animal, and although we
can perhaps draw a few conclusions from basic brain anatomy and
animal work (as I have tried to do), still perfusion after
clinical death at low temperatures with glycerol is bound to have
some major differences from perfusion with blood in life.  We can
learn some of the answers here for certain by watching many
perfusions of the whole cortex of many patients with fiberoptics
and dye systems during less than optimal "field" conditions.  On
the other side of the coin, we can learn something about brain
fine structural deterioration (which is likely to be similar in
all mammals) by doing animal delay experiments at ice temps. 
Lastly, animal experiments of the sort CI and the Russians are
doing (and also we ourselves at BioPreservation) will ultimately
tell us something about how much we gain at the ultrastructural
level by perfusion with cryoprotectants at all.  At some point we
know that besides the extra cracking produced by cryoprotectant,
micro-damage from time at zero Centigrade *waiting* for 
cryoprotectant (and a slow freeze) will outweigh the extra 
micro-damage that occurs due to an immediate "fast" dry ice
freeze with no cryoprotectant.  The question is: when does that
time come?  And how to factor in all the intermediate 
possibilities involving less-than-optimal cryoprotectant surgical
introductions, done at earlier times?

    And what do we do in the meantime?  Real metabolic 
experiments on real brains suggest that the temperature 
sensitivity scale for brain ischemia is not the simplistic factor
of 2 for 10 C sometimes used as rule of thumb by chemists, but
more like a factor of 4 or 5.  Near the ice temp we can expect
something like an equivalent of 1 minute of warm ischemia for
every 1 hour of real-time, or about 24 minutes per day.   One day
on ice alone puts us at about the limit even optimistic 
conventional brain resuscitation workers suggest, due to their
estimates of irreversibility of cell damage.  An additional 1/2
to 1 hour warm-ischemia equivalents is generated even in the best
of circumstances while cooling the patient.  Thus, even one day
of ice preservation after best cooling results in 1 to 1.5 hours
total warm-ischemia equivalent time, and insides of brain cells
and capillary walls are seriously disordered at much beyond this. 
Is any of this structure associated with memory?  We don't know,
but it seems best not to find out.  My best guess is that
anything beyond a day or two at the ice temp, even with an
optimal cooling history and no downtime to speak of, is very
unwise.  If it can be avoided by more rapid (but cruder) 
early perfusion followed by crude dry ice freezing, perhaps it
should be.

                                  Steve Harris

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