X-Message-Number: 27972
Subject: Minimizing Damage to Cryonics Patients
Date: Mon, 22 May 2006 06:14:37 US/Eastern

  I have struggled greatly with problems of understanding
the kinds of damage cryonics patients are subjected to, ways
to minimize this damage and the amount of damage which may
ultimately be reparable by a future technology. Answering these
questions is extremely difficult, demanding much extrapolation
from science not directly applicable to cryonics and
speculation about what future science may be able to do.
Much of what I have written on this subject makes reference
to peer-reviewed journals and uses language that is too
technical for "normal people" to understand.

  Here I am struggling to write an "ordinary language"
summary of my current thinking on the above subjects.
(You should know that a *neuron* is a brain cell,
that *ischemia* is the damage that occurs without blood
flow due to lack of oxygen and nutrient and that 
*mitochondria* are tiny organs inside cells that are
a source of energy.) Those who want more rigorous
justification and references should read the reviews
which form the basis of what I will write here:


and especially


  I am very intent on minimizing damage to cryonics patients,
while believing that cryonics patients may be able to
sustain more damage that is often thought. Brain tissue is
actually quite durable. Experiments on rats have shown that
after cutting-off brain circulation, even after 6 hours
only 15% of the neurons are dead. It takes about 10 hours
for half the neurons to die. Neurons taken from elderly humans
2.6 hours after death and placed in cell culture show that
about 80% of those neurons are still viable after two weeks.
But a "dead" neuron is not necessarily a neuron that cannot
be revived or reconstructed by future technology. After
24 hours mitochondria in neurons can still be distinguished
by electron microscopy studies.

   Cooling makes a big difference. I would estimate that the
effect on brain tissue of five hours at room temperature
(body temperature cooling to room temperature) post-mortem
is about the equivalent of five days in a hospital
refrigerator (2oC to 7oC). Even better preservation would
be expected at water ice temperature (0oC). Salt water is
not recommended, however, because lowering the temperature
below 0oC can result in freezing damage to blood vessels,
which would prevent cryonics organizations from perfusing
with cryoprotectants to minimize freezing damage.

  I not believe that freezing a cryonics patient, ie, cooling
to cryogenic temperature without cryoprotectants, means
that the cryonics patient has no hope of reanimation. Although
brain tissue is greatly scrambled by ice formation, the
scrambling happens in a deterministic manner and is well
preserved at liquid nitrogen temperature. A sufficiently
powerful future technology may be able to unscramble this
well-preserved mess. And some freezings are better than
others. If cooling is done slowly between 0oC and -60oC
ice will form in the extracellular space. Neurons and
synapses will be protected by the fact that there are
few intracellular nucleators for ice-formation and by
the fact that cell contents have some natural
cryoprotectant ability. The cells will, however, suffer
mechanical crushing by extracellular ice.

   There is a five minute limit beyond which CPR usually
cannot prevent eventual brain damage. Part of this problem
is due to increased resistance by blood vessels to blood
flow. CPR cannot achieve blood pressure much above 25mm Hg.
But blood reflow to the brain can be achieved by increasing
perfusion pressure. Even after 30 minutes a perfusion
pressure of 100mm Hg can achieve blood flow in
experiments with cats.

  The other critical aspect of the "5-minute limit" is
apoptosis (cell suicide). After about 5 minutes without
blood flow (no oxygen or nutrient) brain cells begin
the process of killing themselves. This is a very slow
process that takes many hours to complete. A heart
attack victim who has received no CPR for 5 minutes
can usually expect lasting brain tissue injury even
if help comes later. But for a cryonics patient for
which timely cooling has occurred, the cell suicide
process is reduced to slow motion, and may easily be
reversible by a future technology. Even a drop in
temperature from 37oC (body temperature) to 31oC
has been shown to triple the amount of time that
neurons can tolerate ischemia in experiments with

  There is no question that a well-equipped standby team
can more rapidly cool a cryonics patient than would be
expected by a funeral director or family member. In
most of the best Cryonics Institute cases ice is packed
around the patients head within a half-hour of
deanimation. A standby team that is waiting by the
bedside would presumably be able to detect deanimation
quickly, get quick pronouncement of death from a hospice
nurse and begin cooling within minutes.

    Cooling in an ice bath with flowing water is much
more efficient than cooling with ice bags. An ice bath
with circulating water can cool a human body from 37oC
to 25oC in 30 minutes, whereas ice bags would cool
not much lower than 33oC in 30 minutes (depending
on the size of the cryonics patient). A standby
team can restore blood flow with an ACDC mechanical
cardiopulmonary device far more efficiently (and
with greater blood pressure) than can be done with
manual CPR. Stronger blood flow also accelerates
cooling. And the cardiopulmonary device provides
oxygen to help maintain the viability of brain tissue.

  Although I believe that rapid cooling and
cardiopulmonary support are of tremendous benefit for
a cryonics patient, I have been more dubious about
the benefit of medications other than heparin. I do
believe that large quantities of Vitamin E (both
alpha AND GAMMA tocopherol), fish oil, melatonin,
curcumin, N-acetylcysteine and other anti-oxidants
can be of great benefit to a cryonics patient when
given up to the time of deanimation. Post-deanimation
benefits of these substances may not  be so great.

   Another source of my skepticism has been
the minimal benefit of medications for stroke
therapy in clinical studies. One notable exception
to this, however, is thrombolytics (clot-busters).
Thrombolytics given to stroke victims within a
couple of hours of a stroke can double the chances
of a 3-month favorable outcome. Even when given
within 6 hours the chances can be improved up to
20%, but the risk of thrombolytics contributing
to hemorrhage also increases.

  Mike Darwin and Dr. Steve Harris have done
experiments with dogs in which a medication
cocktail reportedly nullified the damaging effects
of up to 17 minutes of time without blood flow.
In support of their claim is the fact that
Dr. Peter Safar, the scientist who "invented"
CPR, did experiments in the 1970s in which
he was able to prevent brain damage in dogs
subjected to 12 minutes without blood flow by
the use of heparin, dextran 40 blood dilution
and epinephrine to elevate blood pressure.

  Another factor to consider is reperfusion
injury. Restoring circulation within 20-30
minutes after the heart has stopped can
benefit brain tissue, but beyond that time
(possibly especially without the benefit of
anti-ischemic medications) restoring the
circulation is more likely to damage brain
tissue than be of benefit. Whereas oxygen
allows mildly ischemic tissue to recover,
oxygen greatly damages more severely
ischemic tissues. Previously I mentioned an
experiment in which neuron mitochondria were
visible in an electron microscope after 24
hours of ischemic time. By contrast, 3 hours
of ischemia followed by 2 hours of reperfusion
resulted in neurons being much more damaged
and mitochondria showing little structure.

  Blood vessels are also greatly damaged by
reperfusion injury, which can compromise
efforts to perfuse with cryoprotectants. For
this reason, the Cryonics Institute no longer
wants funeral directors to do a blood washout
before shipment, even if good organ preservation
solution could replace the blood. Without
standby, rapid cooling and cardiopulmonary
support and with a funeral director not
beginning a washout within an hour of
deanimation, there is a great likelihood of
considerble reperfusion injury.

  In conclusion, although I think that
cryonics patients can sustain considerable
ischemic time and freezing damage without
losing hope for future revival, I think it
is prudent to minimize damage if possible
and affordable. Minimizing damage not only
increases the probability of future reanimation
from a technical point of view, but it means
that reanimation would be sooner rather than
later. The later the reanimation, the
greater the chance that unfavorable events
will interfere with cryopreservation.

  -- Ben Best, President, Cryonics Institute

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