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I have struggled greatly with problems of understanding the kinds of damage cryonics patients are subjected to, ways to minimize this damage and the amount of damage which may ultimately be reparable by a future technology. Understanding these issues can be difficult. It demands much extrapolation from science not directly applicable to cryonics and speculation about what future science may be able to do. Much of what I have written elsewhere on this subject makes reference to peer-reviewed journals and uses language that is too technical for people without a strong background in biological science to understand.
Here I am struggling to write an "ordinary language" summary of my current thinking on the above subjects. (You should know that a neuron is a brain cell, that ischemia is the damage that occurs without blood flow due to lack of oxygen and nutrient and that mitochondria are tiny organs inside cells that are a source of energy.) Those who want more rigorous justification and references should read the reviews which form the basis of what I will write here:
Ischemia and Reperfusion Injury in Cryonics
and especially
Quantifying Ischemic Damage for Cryonics Rescue
I am very intent on minimizing damage to cryonics patients, while believing that cryonics patients may be able to sustain more damage that is often thought. Brain tissue is actually quite durable. Experiments on rats have shown that after cutting-off brain circulation, even after 6 hours only 15% of the neurons are dead. It takes about 10 hours for half the neurons to die. Neurons taken from elderly humans 2.6 hours after death and placed in cell culture show that about 80% of those neurons are still viable after two weeks. But a "dead" neuron is not necessarily a neuron that cannot be revived or reconstructed by future technology. After 24 hours of ischemia mitochondria in neurons can still be distinguished by electron microscopy.
Cooling makes a big difference in improving brain preservation. I would estimate that the effect on brain tissue of five hours at room temperature (body temperature cooling to room temperature) post-mortem is about the equivalent of five days in a hospital refrigerator (2ºC to 7ºC). Even better preservation would be expected at water ice temperature (0ºC). Salt water is not recommended, however, because lowering the temperature below 0ºC can result in freezing damage to blood vessels, which would prevent cryonics organizations from perfusing with cryoprotectants to minimize freezing damage.
I do not believe that freezing a cryonics patient, ie, cooling to cryogenic temperature without cryoprotectants, means that the cryonics patient has no hope of reanimation. Although brain tissue is greatly scrambled by ice formation, the scrambling happens in a deterministic manner and is well preserved at liquid nitrogen temperature. A sufficiently powerful future technology may be able to unscramble this well-preserved mess. And some freezings are better than others. If cooling is done slowly between 0ºC and −60ºC ice will form in the extracellular space. Neurons and synapses will be protected by the fact that they don't contain many intracellular nucleators which can cause ice-formation and by the fact that cell contents have some natural cryoprotectant ability. The cells will, however, suffer mechanical crushing by extracellular ice.
There is a five minute limit after cessation of heartbeat (ischemia, no oxygen or nutrient being delivered in blood) beyond which CPR usually cannot prevent eventual brain damage. Part of this problem is due to increasing resistance by blood vessels to blood flow with the passage of ischemic time. CPR cannot achieve blood pressure much above 25 mm Hg. But blood reflow to the brain can be achieved by increasing perfusion pressure. Even after 30 minutes without blood flow a perfusion pressure of 100 mm Hg can restore blood flow in experiments with cats.
The other critical aspect of the "5-minute limit" is apoptosis (cell suicide). After about 5 minutes without blood flow brain cells begin the process of killing themselves. This apoptosis is a very slow process that takes many hours to complete. A heart attack victim who has received no CPR for 5 minutes can usually expect lasting brain tissue injury even if help comes later. But for a cryonics patient for which timely cooling has occurred, the cell suicide process is reduced to very slow motion, and may easily be reversible by a future technology. Even a drop in temperature from 37ºC (body temperature) to 31ºC has been shown to triple the amount of time that neurons can tolerate ischemia in experiments with gerbils.
There is no question that a well-equipped cryonics standby team (standing by the bedside of a terminal cryonics patient) can more rapidly cool a cryonics patient than would be expected by a funeral director or family member. In most of the best Cryonics Institute cases ice is packed around the patients head within a half-hour of deanimation (legal death). A standby team would presumably be able to detect deanimation quickly, get quick pronouncement of death from a hospice nurse and begin cooling within minutes.
Cooling in an ice bath with flowing water is much more efficient than cooling with ice bags. An ice bath with circulating water can cool a human body from 37ºC to 25ºC in 30 minutes, whereas ice bags would cool not much lower than 33ºC in 30 minutes (depending on the size of the cryonics patient). A standby team can restore blood flow with an ACDC mechanical cardiopulmonary device far more efficiently (and with greater blood pressure) than can be done with manual CPR. Stronger blood flow also accelerates cooling. And the cardiopulmonary device provides oxygen to help maintain the viability of brain tissue.
Although I believe that rapid cooling and cardiopulmonary support are of tremendous benefit for a cryonics patient, I have been more dubious about the benefit of medications other than heparin. I do believe that large quantities of Vitamin E (both alpha AND GAMMA tocopherol), fish oil, melatonin, curcumin, N-acetylcysteine and other anti-oxidants can be of great benefit to a cryonics patient when given up to the time of deanimation. Post-deanimation benefits of these substances may not be so great.
Another source of my skepticism has been the minimal benefit of medications for stroke therapy in clinical studies. One notable exception to this, however, is thrombolytics (clot-busters). Thrombolytics given to stroke victims within a couple of hours of a stroke can double the chances of a 3-month favorable outcome. Even when given within 6 hours the chances can be improved up to 20%, but the risk of thrombolytics contributing to hemorrhage also increases.
Mike Darwin and Dr. Steve Harris have done experiments with dogs in which a medication cocktail reportedly nullified the damaging effects of up to 17 minutes of time without blood flow. In support of their claim is the fact that Dr. Peter Safar, the scientist who "invented" CPR, did experiments in the 1970s in which he was able to prevent brain damage in dogs subjected to 12 minutes without blood flow by the use of heparin, dextran 40 blood dilution and epinephrine to elevate blood pressure.
Another factor to consider is reperfusion injury. Restoring circulation within 20-30 minutes after the heart has stopped can benefit brain tissue, but beyond that time (possibly especially without the benefit of anti-ischemic medications) restoring the circulation is more likely to damage brain tissue than be of benefit. Whereas oxygen allows mildly ischemic tissue to recover, oxygen greatly damages more severely ischemic tissues. Previously I mentioned an experiment in which neuron mitochondria were visible in an electron microscope after 24 hours of ischemic time. By contrast, 3 hours of ischemia followed by 2 hours of reperfusion resulted in neurons being much more damaged and mitochondria showing little structure.
Blood vessels are also greatly damaged by reperfusion injury, which can compromise efforts to perfuse with cryoprotectants. For this reason, the Cryonics Institute no longer wants funeral directors to do a blood washout before shipment, even if good organ preservation solution could replace the blood. Without standby, rapid cooling and cardiopulmonary support and with a funeral director not beginning a washout within an hour of deanimation, there is a great likelihood of considerable reperfusion injury.
Although I think that cryonics patients can sustain considerable ischemic time and freezing damage without losing hope for future revival, I think it is prudent to minimize damage if possible and affordable. Minimizing damage not only increases the probability of future reanimation from a technical point of view, but it means that reanimation would be sooner rather than later. The later the reanimation, the greater the chance that unfavorable events will interfere with cryopreservation.