From: Mgdarwin@cs.com
Date: Fri Mar 03 2000 - 16:49:41 MST
John,
>>>>>>The complexity of these problems is very large and you are
unlikely to have single individuals who can "grok" the entire
range of possible damages (and solutions). Solution: Cryonicists
should establish a network of individuals, each of which is *the*
expert on the state of the art with regard to various pathologies
(calcium influx, free radical damage, mitochondrial swelling,
neutrophil activation). Only if you have individuals who are expert in these
areas who are able to converse regularly will you begin to see progress in
pre &
post-suspension methods.
I'll emphasize this point by observing that Mike's concerns about
arachidonic acid and iron might be dealt with by aspirin and
desferoxamine respectively.>>>>>>
Chuckle.
I tried deferoxamine almost 20 years ago; it is still a standard part of the
cryonics transport protocol. In general, you are right: I've chosen to
specialize in ischemia reperfusion injury of the whole body (turns out the
brain's a piece of cake out to 20 minutes of arrest time, at least). I' HAVE
become an expert on neutophils, platelet activating factor, PMNL adhesion,
protease inhibition, and much more. As a result, we get dogs back from 17
minutes of total cardiac arrest at normothermia 75% of the time with zero
neurological deficit. In fact, these are the smartest dogs in the colony.
The barrier now is sepsis-mediated multisystem organ failure which I believe
is occuring as a result of necrosis of the tips of the intestinal microvilli
(which are marginally oxygented at ~10 torr, even under basal conditions).
Unfortunately, the pressors and other druhgs we must give, and the "shock"
response from cardiac arrest results in prolonged vasoconstriction of the
gut, meaning that it gets not just 20 minutes of ischemia, but more like
2-hous We think we've got this problem licked, and will hopefully be going
back into the lab in a few weeks to see if this is so. Then we'll push out to
30 minutes.
The next model is a really neat one: exsanguinating trauma. This is nice
because you have the opportuity to give huge amount of solution IV BEFORE the
insult. Needless to say that solution will contain all the drugs that work
AFTER the insult, and lots more as well. Preliminary data in acute models
indicates that with this sort of "premedication" we can achieve a state of
normothermic "suspended animation" of at least an hour. If we cool, probably
a lot longer. Considering that the typical trauma victim who bleeds to death
before reaching the OR (~20,000/yr in the US) gets about 10-15 liters of
crystalloid, if we cooled that 10 liters to O degrees C on infusion he'd be
down (70 kg avaerage man) ~3-5C by the time he arrested. Brain temps would
probably be lower because systemic circulation is shunted preferentially to
the brain and heart in shock. It's very exciting reserch.
Cropreservation rsearch is proceeding in a similar fashion elsewhere. Other
experts are working on the problem, with a similarly rapid rate of progress.
At some point our inights may be of benefit to them, and vice versa (we both
have the blood brain barrier to deal with).
The point is, WORK is the answer, not debates about the things that typcally
go on amongst those on Cryonet. At least it is the answer if you don't want
to wait till the Omega point and you value life NOW and time lost to recovery
as TIME LOST. That's up to the individual. Me, I value TIME LOST NOW, and I
associate cryopreserved down-time with RISK of the greatest kind.
It is a volatile, unstable world we live in (having just retuned from 2 solid
months traveling it in the 3rd world) and it is better to be ale to run and
think than sit around in a big, heavy stainless steel tank of LN2 pushinh up
bubbles.
It is also funny how these theoretical debaters about Omega points and the
fundamental nature of information loss as it relates to the structure of the
universe get REALLY uptight when THEY start to die and are staring the
freezer in the face. Then the begging and wishing and hoping REALLY start in
earnest. "How soon do you think I will be revived? What about my kids, what
about my wife? How much memory do you think might be lost? Funny how the
theoretical becomes of such immediate practical concern when all the things
you don't consider valuable about life in academic discussions are about to
be taken away from you, and just MAYBE for forever. You'll just have to take
my word for it on this one: I've seen it all to often. After 30 years' worth
of handholding the likes of such Angel Dancing theoreticians I decided to
spend my time on prolonging the lives of people who at least know and value
what they have, and are willing to pay for more of it, and don't slap you in
the face as you try to help them get it.
Mike Darwin, Director of Reseach
Critical Care Reserch, Inc.
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