X-Message-Number: 11509
Date: Sun, 4 Apr 1999 10:52:06 -0700 (PDT)
From: Doug Skrecky <>
Subject: erythritol prefeeding may enable reversible cryopreservation

   Cryoprotectant toxicity appears to be the primary barrier to successful
 cryopreservation of intact organs, or even entire bodies. Currently the
 time required to perfuse vitrifiable amounts of toxic cryoprotectants
 into organs precludes organ viability. Here's an idea which I believe may
 have been overlooked, which may help to make an end-run around this
 conundrum. An experiment is suggested to test the value of this idea.
   Not all cryoprotectants exert significant toxic side-effects. However
 as far as I am aware all of the "non-toxic" cryoprotectants have
 relatively poor permeation past cell membranes, and thus would be time
 consuming to perfuse with. Since only a limited time is available for
 perfusion before irreversible anoxic damage occurs postmortum, my idea is
 to administer these premortum. With significant amounts of non-toxic
 cryoprotectants in bodily tissues before deanimation we would have a
 significant advantage; a head start as it were - in the race to perfuse
 vitrifiable quantities of cryoprotectants postmortum before irreversible
 damage occurs.
   Among the non-toxic cryoprotectants which are not readily metabolized
 in vivo, the one with the greatest absorption from the digestive system
 (and the highest membrane permeability) is erythritol. This had been fed
 to rodents chronically at 20% in the diet (45 gm/kg body weight) with
 side effects no more serious than a transient diarrhea. (Regulatory
 Toxicology and Pharmacology 24: S191-S197 1996) Erythritol is rapidly
 excreted, but some is retained in all organs. (Regulatory Toxicology and
 Pharmacology 24: S206-S213 1996) Humans have been fed erythritol at 1
 gm/kg with no side effects. (Regulatory Toxicology and Pharmacology 24:
 S286-S295) 1996)
   How high chronic feeding of erythritol can be before serious side
 effects are encountered is unknown. I would like to suggest an experiment
 be done with rodents to see how high the oral dosage can be pushed, then
 the organs harvested and tested for their viability after freezing under
 various cryoprotectant perfusing protocols.
   The analogy I would like to draw here is as follows: With a shuttle
 launch into a stable earth orbit being equated with reversible
 cryopreservation of entire organs/bodies, using a chronic high dose
 erythritol prefeeding regimen would be like using a 747 airplane to
 launch a space shuttle. The retained erythritol in tissues would raise
 the platform of the initial launch off the ground and into the air, where
 a stable orbit would be more likely with a given amount of fuel for the
 shuttle. Currently the amount of fuel (cryoprotectants) that can be
 safely loaded into the shuttle (body) is insufficient to attain orbit
 from a ground launch. Prefeeding erythritol would eliminate the need for
 a ground based launch, since some cryoprotectants would already exist in
 tissues even before perfusion is commenced.
   Any comments, anyone?

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