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? Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=11509