From: Eugene Leitl (eugene.leitl@lrz.uni-muenchen.de)
Date: Mon Jun 19 2000 - 23:45:16 MDT
Robert Bradbury writes:
> Getting through the skull is a minor problem I presume... Or have
> you removed the brain and spine???
Cutting is a seriusly bad idea (if you really want it, then why not
LN-cooled isotopically pure diamond knifes? ;) -- you wouldn't want to
cut a platter full of porridge, wouldn't you? I recommend going to
your local slaughterperson, and obtain a relatively fresh animal
brain. Try moving it, and handling it. It does really tell you a lot
more than theoretizing about an object one has never held in one's
hands.
Of course, one can dremel the skull open after perfusion with
cryoprotectants, but it's tedious (=slow, and can be a source of
mechanical injury), and the brain will tend to deform under its own
weight because of lack of floatation due to absence of
liquor. (Dremelling in a vat of liquid is a nighmare, at least for
current humans -- sonar/touch guided robots might be different, but
who's going to develop them?). It takes forever, is surprisingly
messy, but is probably useful if you want to vitrify the brain
(viscosity will soon prevent you from anything put passive thermal
conduction cooldown).
If there is really a threshold where current vitrification agents
can't cool down human sized brain cleanly before massive nucleation
occurs (I'm only talking about vitrification here, obviously), you
could always attempt to bisect it *very* carefully. But, I don't think
this is an issue at all. Use conservative approach, unless it's
obviously failing. Do not hurt the patient unnecessarily, that's what
experimental animals are for.
> I doubt the cooling rate matters much. There is still residual brain
> activity in comatose patients or patients who have been dead for hours.
Well, your EEG is sure flat <20 s after you arrest. At that point
you've burned all your local ATP and the oxygen.
> Since the brain is sterile you aren't going to have bacteria consuming
> anything (as would be the case in the gut). Since you are out of ATP
> you can't do any breakdown (or construction) that requires energy.
> So so long as the non-energy requiring enzymes in compartments like
> the lysosomes remain in their compartments, not much is going to happen.
Ideally, there should be no arrest. (Of course that's currently quite
illegal, so we're being purely theoretical here). You would want to
keep perfusability as long as possible. For instance, as soon as you
run out of ATP (abovementioned ~20 sec), cells can't maintain ion
equilibrium, and tissue suddenly start to swell, ruining your
perfusion infrastructure by closing up capillaries and vessels. There
are subjective differences, but from a certain minimal duration the
patient has clotted (unless given heparine etc. before the event), and
you just can't perfuse. Then, straight freeze is your only
hope. Personally I think that's snake oil, but that's just me.
> The only caveat here is whether the accumulation of CO2 in the brain
> lowers the pH enough to create an acidic enough environment outside
> the lysosomes to activate the enzymes that haven't been delivered
> to those organelles yet. [An area where the people interested
> in Cryonics should do some further study.]
Interesting thought. Of course, pH is being homeostated if you keep
you on life support, as you should. Apparently, the gut/mucosa suffers
extensive damage during ischaemia, which really limits sustained
recovery. You can't impress the mainstream with excellent structural
preservation if your animal is very dead.
> I don't disagree that the razor-blade approach might cool things faster
With most recent (research-grade, patients must pass for now)
protocols cooling at least rabbit-head samples to vitrify
quantitatively appears to be very possible. As a litmus test,
rewarming shows surprisingly little nucleation. Huge progress is being
made recently in R&D, purportedly technology transfer is progressing
without too much red tape, so let's keep our fingers crossed.
> and the computer probably could stick things back together, it seems
Sticking them together is not a problem, but your interfaces are all
mush (=information erasure). Why, if you don't have to?
> better however to keep the ultrastructure as intact as possible even
> at the expense of a lower cooling rate, unless severe extralysosomal
> degradation is occuring.
Cooling down buys you time. After you go way below zero, you have to
be quick, or things start to nucleate. So, there are two phases.
> It isn't the blood(O2/glucose)-loss that damages the brain, its
> the resupplying of energy resulting in excitotoxicity within the
> neurons causing them to lose control of ion storage and really
Oh yes, EEG goes all wild if you reperfuse an ischaemically damaged
brain. Because of this, you have to inhibit self-destructive activity
by using a plethora of drugs as well as hypothermy.
> make a mess of things (I'm sure Anders could provide a more
> technical explanation -- there is probably several sites on the
> net that discuss this as well). Since brain reanimation will be
> a carefully controlled process, this is unlikely to occur. We
No one is going to reperfuse, and reanimate. You'd want to stay in
solid state as long as possible, because if things start to flow you
lose control. In theory, you can disassemble the patient, remove
artefacts with a digital filter on the fly, add fractal retractable
heat exchanger, and then rebuild the whole thing. However, technology
as advanced as that means there is no point in reviving the patient,
just upload him, and save resources. Running a whole ecosphere bubble
in slowtime is expensive.
> may have drugs within the next 5-10 years that suppress this
> situation and in the more distant future nanobots within or around
> neurons can obviously handle the problems.
We do have very nifty drugs already, but you really need to
pre/postmedicate the patient, and do not allow any noticeable
ischaemic damage to occur. Ideally, cryonics procedures should take
over with no hiatus when classical medicine fails. In many cases,
euthanasia does really make sense, I really hope future legislation
will address that, despite current trend to overregulation and a
society *still* growing litigation-happy year by year.
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