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The purpose of cryonics protocol is to minimize or eliminate cryopreservation damage in order to maximize the chance that a cryonics patient can eventually be restored to life, cured of all disease and even brought to a condition of enduring health & youth. Cryonics protocol is discussed in great detail on several pages of this website, but a short summary can serve the purpose of providing perspective for understanding the details. (For more background on cryonics see my essay Cryonics: Frequently Asked Questions (FAQ).)
Cryonics protocol between legal declaration of death and long-term storage at cryogenic temperatures can be divided into four stages:
(1) initial cooldown while providing cardiopulmonary support
(2) blood washout, replacing blood with organ preservation solution
(3) perfusion with cryoprotectant
(4) cooldown to cryogenic temperatures
For cryonics to work brain tissue must be either preserved intact or damaged in such a way that it can be repaired. A broken vase or an automobile with a flat tire can be repaired, but a vase dissolved in a vat of acid cannot be repaired. Cryonicists distinguish between damage and destruction, recognizing that destruction is irreparable and recognizing that some forms of damage may be irreparable today, but may be capable of being repaired by future molecular repair technology. Although freezing damage may someday be repaired, brain damage due to Alzheimer's Disease may be irreparable. A person who has died in their sleep and is not discovered for days probably has irreparable destruction of brain tissue.
If a person is declared legally dead immediately upon cessation of heartbeat & respiration, nearly all of the cells in that person's brain may still be alive. Organ transplantation would not be feasible were it not for the fact that legal death does not declare the death of all cells, tissues and organs -- including the brain.
But within 5-10 minutes without oxygen or nutrient degenerative processes begin in the brain. The main initial degenerative processes, however, are in the circulatory system -- blood agglutination and vascular spasm. Brain ultrastructure can actually be maintained up to one hour without oxygen or nutrient. Attempts to restore blood circulation within even 10-15 minutes can be damaging. In reperfusion injury restoration of circulation after a long delay actually causes the blood oxygen to oxidize tissues rather than revive them.
Within a few hours at room temperature ischemic injury, release of arachidonic acid from membranes and lactic acid produced by anaerobic metabolism (metabolism in the absence of oxygen) increases the acidity of tissues, including brain tissue. Lysosomes (acidic organelles containing hydrolytic enzymes) burst, further degrading tissue. Anaerobic clostridium bacteria (gangrene) accelerates tissue degredation. Within 24 hours at room temperature a dead person's brain will have virtually dissolved. Cryonics procedures must be applied much sooner for there to be a reasonable hope of success.
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Under ideal circumstances a cryonics patient who has not experienced much brain damage from disease or aging will be declared legally dead in a hospital or hospice setting with a cryonics emergency-response team standing by. Currently, only a small fraction of cryonics cases occur under these conditions, but there is hope for improvement.
With a death certificate signed almost immediately following cessation of heartbeat & respiration, a cryonics team restores heartbeat & respiration with CPR and a heart-lung machine to keep the cells of the patients organs & tissues alive. Manual CPR can provide one-third the circulation of a heart, and is quickly tiring. A heart-lung machine can provide two-thirds the circulation of a heart, giving much better oxygenation.
The patient should be cooled from body temperature (37ºC) to 10ºC as quickly as possible, since each 10ºC temperature drop cuts metabolic rate in half. Cooling is most effective when applied to the head, neck, groin and underarms due to the concentration of blood vessels close to the surface in those areas. Cooling is most rapid when applied as a cold flowing liquid applied to a broad surface. Flowing ice-water from a squid-like device cools much more rapidly than ice bags. Comparative time (depending on patient size) to cool to 10ºC would be in the range of:
ice bags -- 5 hours
ice bath -- 3 hours
squid -- 2 hours
The artificial circulation established during initial cooldown can allow for the delivery of medications to the patient's bloodstream which will reduce tissue degradation and facilitate cryopreservation. Such medications include heparin (to prevent blood coagulation), dextrose (nutrient) and antioxidants (to reduce ischemic injury). (For a more complete list see cryonics medications.)
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Once the patient has reached 10ºC the blood should be removed. At 10ºC the metabolic rate has declined enough and the oxygen carrying capacity of water has increased enough that blood is no longer needed. (Water near freezing temperature can hold nearly three times as much dissolved oxygen as water near boiling temperature.) Moreover, at 10ºC blood begins to agglutinate, impeding circulation. Blood must be replaced with isotonic (saline-like) solution which will prevent osmotic shrinking or swelling of cells & tissues. The blood replacement solution should also contain nutrient as well as an ingredient like HydroxyEthyl Starch (HES) which (like blood albumin) prevents tissue edema. Viaspan -- a commercial product used for preserving organs being saved for transplant -- fits the criteria for a cryonics blood washout solution. (For more details, see Blood Washout & Replacement.)
In some cases washout is begun before reaching 10ºC. The lower oxygen carrying capacity of water at higher temperatures will be compensated-for by the fact that the washout cah be done with a very cold solution, thereby accelerating the cooling rate.
A cryonics patient perfused with an organ preservation solution can be shipped at water-ice temperature to a cryonics facility without substantial tissue damage as long as the shipment time is less than a half-day. In some circumstances, as in rushing for a plane, blood washout has been skipped altogether on the theory that as long as heparin is preventing coagulation the washout step may cost more time than it is worth -- and on the theory that blood can preserve tissues as well as an organ preservation solution. The question concerning "how long is too long" for a patient at low temperature to go without circulation during shipping before tissues are damaged has typically been on circulatory adequacy. If the time is more than about 18 hours, injury to the circulatory system is too great to prevent good perfusion. (The prior condition of the patient will also be a factor, of course.)
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Cryoprotectants are antifreeze agents -- agents to prevent ice formation and ice-crystal damage. Cryoprotectant mixed with water results in a solution that gradually solidifies as a syrupy glass rather than crystallizes -- a process known as vitrification. Common cryoprotectants include:
ethylene glycol -- automobile antifreeze
propylene glycol -- eliminate ice-cream ice-crystals
glycerol -- blood, sperm
DMSO -- embryos
Glycerol has been used to preserve sperm & blood since around 1950. Glycerol has been used in cryonics for most of cryonics history. But like most cryoprotectants, glycerol can be toxic at high concentrations. Moreover, glycerol will not completely vitrify at a concentration less than 55%v/v -- which is too viscous for cryonics perfusion.
Recently, cryoprotectant mixtures have been developed at 21st Century Medicine (21CM) which are being used at Alcor to cryopreserve neuro (head-only) cryonics patients with less than 0.2% ice formation. Toxicity is so low that hippocampal slices in experimental rats have been cryopreserved to -140ºC and rewarmed with 100% viability. Rapid cooling & ice-blockers have provided the crucial assistance which has made brain vitrification possible. Cryobiologist Dr. Yuri Pichugin at the Cryonics Institute has developed a similar vitrification solution.
10ºC seems to be an optimal temperature for cryoprotectant perfusion. Perfusion will be through the femoral artery/vein, direct access to the heart or (for a neuro patient) directly through the carotids arteries. (For more details on the perfusion process, see Perfusion & Diffusion in Cryonics Protocol.)
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Silicone oil can remain liquid to nearly -100ºC. Whole body patients at Alcor were cooled in a silicone oil bath at a rate of 0.1ºC For an Alcor neuro patient perfused with vitrifying cryoprotectant, cooling to a solidification temperature (about -120ºC) should be as rapid as possible. The head is placed in a chamber that circulates high velocity nitrogen gas at -135ºC -- which cools at a rate of 0.4ºC per minute. For other patients -- and for neuro patients being cooled from -120ºC to -196ºC (liquid nitrogen temperature), cooling must be slower to avoid cracking from thermal stress. The Cryonics Institute has built computer-controlled cooling boxes which cool to liquid nitrogen temperatures at varying rates as directed by software. (For more details see Computer-Controlled Cooling Boxes at CI.) Cooling of vitrified tissues should be quick before -120ºC (solidification temperature) to prevent ice formation, and very slow below that temperature to minimize cracking due to thermal stress.
Plans are being made to maintain vitrified neuro patients at -140ºC, but it is questionable that this can be done as cheaply or securely as liquid nitrogen storage. Liquid nitrogen is much less expensive and readily-available than any substance with a boiling temperature near -140ºC. Cryonics patients are stored in "thermos bottles" (dewars) that boil-off slowly -- only needing to be topped-off every few weeks. Electrical cooling is more vulnerable to mechanical or power failure -- and is much more expensive.
It would be good to avoid cracking, but cracking may well be a form of damage that can be repaired by future technology. However, the more damage that can be eliminated -- and the less reliance on future technology -- the better the prospects for cryonics patients. (For more details on issues associated with cryonics cooling, see my essay Physical Parameters of Cooling in Cryonics.)
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