X-Message-Number: 29349
From: "Brian Wowk" <>
Subject: Ice blockers and the blood brain barrier
Date: Fri, 23 Mar 2007 19:38:01 -0700

In Cryomsg #29342 Tim Freeman wrote:

>At

>  http://www.cryonics.org/research/CI-VM-1.html

> it says that Pichugin tested 21CM's ice blockers and didn't get
> interesting results.  The most interesting sentence there is:

>>Dr. Pichugin does not believe that these increments of increased
>>viability with ice blockers justify the increase in viscosity or cost
>>if they were added to the CI-VM-1 formula, especially in
>>light of the fact that ice blockers cannot cross cell membranes or the
>>blood-brain barrier.

> Is it true that 21CM's ice blockers don't cross the blood-brain
> barrier?  If so, then how can they be useful?

        It is true that polymers don't cross an intact blood-brain barrier
(BBB).  But they are still useful by two mechanisms.  As Jordon Sparks
indicated, the first mechanism is that they substitute for water in the
cryoprotectant solution, thereby osmotically drawing water out of the brain
through the BBB which helps prevent the brain from freezing.  The second
mechanism by which ice blockers are specifically useful is that they protect
against the formation of ice inside blood vessels that would otherwise grow
into the brain.

        Also, it should be noted that the BBB is often not intact in
cryonics because it is compromised by ischemia.  Wherever the BBB is
compromised, ice blockers will penetrate and protect against ice nucleators
(rogue proteins and other impurities that trigger ice formation) that will
also penetrate into the brain through a compromised BBB.

         With respect to your statement that CI "didn't get interesting
results" with 21CM ice blockers, there are several points that need to be
kept in mind.

1)  CI's toxicity test compared 55% VM-1 to 52% VM-1 at -20oC for only a
10 minute exposure period.  Under these test conditions, the slices were not
exposed to vitrifiable levels of VM-1 throughout.  For hippocampal slices to
become vitrifiable, they must be exposed to CPAs for at least 20 min and
preferably for longer periods.  As time increases, toxic effects also
increase, and therefore the difference between the two solutions will be
greater when they reach the point of actually being vitrifiable.

2)  CI doesn't perfuse people with 55% VM-1, they perfuse them with 70%
VM-1.  If the toxicity of 70% VM-1 had been compared to, say, 65% VM-1 plus
ice
blockers, the difference would presumably be greater than what was found at
55% vs 52% VM-1, because toxicity also increases as concentration increases,
and more and more steeply as concentration rises.

 3)  We find that, in kidneys, eliminating ice blockers is untenable because
even though this reduces the viscosity of the solution, it nevertheless
reduces stability against ice formation to an unacceptable degree.  This
indicates that, on balance, the tradeoff between ice control and viscosity
is decisively in favor of ice control.

         I have confined my answers to the narrow issues you raised rather
than getting into a longer discussion about the differences between CI and
Alcor's solutions and protocols.  It should be understood that no
vitrification solution that currently exists is capable of preserving a
human brain with functional viability by current measures, so extrapolation
and guesswork are involved in the design of any vitrification solution for
cryonics.  I think CI's vitrification solution is a reasonable solution
given the tight cost constraints of their low funding minimums.  I think
Yuri has done good work that few others could do.

---Brian Wowk

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