To Treat the Dead - a paradigm change

[BenTC]

I think its fairly widely accepted that if you go without oxygen for more than a few minutes, you are unrecoverably dead.

Actually, thats not so.

Apparently lack of oxygen doesn't kill. Reperfusion kills. With therapeutic hypothermia you can potentially go an hour without oxygen and recover with no brain damage. I feel that the way this paradigm change could potentially affect peoples lives makes it important to disseminate.

See:
http://www.newsweek.com/id/35045
and Moment Of Death > Video:
http://channel.nationalgeographic.com/s ... b-Overview

I like this as an example that something so widely taken for granted might be so wrong. Its such a paradigm changer in the time allowed to reach medical help that its scary wondering how long this will take to filter down to my health care system. Further information at the University of Pennsylvania Department of Emergency Medicine's Center for Resuscitation Science. Here is their protocol for therapeutic hypothermia and similar.

[Skipjack]

Hmm, so here in Austria, patients are already put into neuroprotective cooling in some cases. It happened to me when I had my heart attack.
But yes, cooling people down until they can be taken care of in a hospital, might indeed be a good idea. Have every ambulance cary a load full of dry ice?

[MSimon]

Some one must have been taking lessons from General Bullmoose.

http://www.lil-abner.com/other.html

[BenTC]

Have every ambulance cary a load full of dry ice?

Close.
They aim for ambulances to carry IV slurry at 4 degrees Celsius. Simple technology. Just the protocols need to be developed.

[BenTC]

Similarly, they have been able to induce suspended animation in mice using small doses of hydrogen sulphide.
http://www.sciencedaily.com/releases/20 ... 083254.htm

[Diogenes]

I haven't been following this thread very closely. Has this been covered ?

http://www.smh.com.au/news/health-and-f ... 39997.html





And another take.


http://www.newscientist.com/article/mg1 ... -hold.html

HASAN ALAM gazes over the cold, motionless body of a pig lying on a stainless steel table before him. The animal has no pulse, no blood, no electrical activity in its brain, and its tissues consume no oxygen. It has been in this state for two-and-a-half hours. It looks dead. "You would think so," he says, "but you can bring it back."

Alam keeps the pig in suspended animation for 90 minutes, long enough to repair its damaged blood vessels. He then warms the pig's blood stored earlier and reintroduces it to bring the pig back to life.

[BenTC]

Interesting articles. A bit different from mine.

• My ref about Becker induces 33 degreeC Mild Hypothemia for the purpose of preventing the self-destruction of cells after oxygen is reintroduced. Its specifically for heart attacks and I speculate also drowning, and not suitale for hemorrhaging patients.
• Your ref about Alum induces 10degreeC Profound Hypothermia to treat hemorrhaging trauma patients. The lower temperature has more complications but it turns off the oxygen damage all together.
• Note, I read that 4 degreesC is where cells start to rupture due to temp.

Here are some extracts from a current article by Alum "Hypothermia in bleeding trauma: a friend or a foe? Dec2009"
...
For 34-36°C, controlled decreases in core body temperature are associated with decreased metabolic and oxygen demands in tissues [3], reduced activation of cell death pathways, and blunted inflammatory and immune response.
...
Hypothermia decreases the enzymatic activity of clotting factors and reduces the number and function of platelets [114]. This effect is dependent upon the depth of hypothermia and becomes clinically measurable when core temperature drops below 33°C [- ie cooling makes it harder to stop hemorrhaging.]
...
[From large animal study] Maximum benefits are achieved when profound hypothermia is induced rapidly (2°C/min) and reversed more slowly (0.5°C/min). Optimal depth has also been shown to be 10°C with decreased survival demonstrated at ultra profound temperature (5°C) [152]. In our experiments, rewarming was active and begun promptly after hemorrhage was controlled using cardiopulmonary bypass with the use of blood products as needed to reverse coagulopathy and restore normal oxygen delivery. We delayed blood transfusion until after injuries were repaired and metabolic demands were increased in the re-warming period. Using this optimized model, 60 min of profound hypothermia achieved 90% survival in a model that is 100% lethal in normothermic animals. Uniquely, coagulopathy and intraoperative bleeding are not a major problem during profound hypothermia since tissue viability is independent of oxygen delivery. Profound hypothermia renders coagulopathy and bleeding irrelevant.

* mild (33-36°C), moderate (28-32°C), deep (16-27°C), profound (6-15°C), and ultra-profound (<5°C) hypothermia

[kurt9]

I think its fairly widely accepted that if you go without oxygen for more than a few minutes, you are unrecoverably dead.

Actually, thats not so.

Apparently lack of oxygen doesn't kill. Reperfusion kills. With therapeutic hypothermia you can potentially go an hour without oxygen and recover with no brain damage. I feel that the way this paradigm change could potentially affect peoples lives makes it important to disseminate.

Duh! This have been obvious to us since the mid 80's when the guys I know at Alcor did their dog experiments.

As long as the neuro-structure of the brain is intact, you are still potentially alive, even if current medical technology cannot repair the problem that made you disfunctional (e.g. aging, cancer, cardiovascular). The purpose of bio=preservation is as a form of "medical time travel", to get you to the time where technology has developed such as to repair problems that currently will kill you.

www.alcor.org
www.suspendedinc.com

[BenTC]

Duh! This have been obvious to us since the mid 80's when the guys I know at Alcor did their dog experiments.

Theoretically yeah. Animal experiments, fine.
But Duh? How then is it that hospitals the world around currently have it so wrong?

With this realization came another: that standard emergency-room procedure has it exactly backward. When someone collapses on the street of cardiac arrest, if he's lucky he will receive immediate CPR, maintaining circulation until he can be revived in the hospital. But the rest will have gone 10 or 15 minutes or more without a heartbeat by the time they reach the emergency department. And then what happens? "We give them oxygen," Becker says. "We jolt the heart with the paddles, we Blood-starved heart muscle is suddenly flooded with oxygen, precisely the situation that leads to cell death. Instead, Becker says, we should aim to reduce oxygen uptake, slow metabolism and adjust the blood chemistry for gradual and safe reperfusion.
http://www.newsweek.com/id/35045

So from Alcor

Another project was a study of cat brains. These were perfused and frozen under a variety of conditions, in an effort to assess problems that would occur in human suspensions. Examinations were made at the macroscopic, histological (cellular) and ultrastructural levels. Results showed that, while fine structure clearly was being preserved, the preservation was not perfect. Basic questions remained unanswered, such as whether identity-critical information would be adequately retained in frozen brain tissue. (These questions are still unanswered and await better understanding of how memories are stored.)
http://www.alcor.org/Library/html/researchhistory.html

Inability to Verify Results
Suppose a patient experiences 30 minutes of warm ischemia (lack of blood flow at near-normal body temperature) after legal death occurs. Will this downtime create damage that is irreversible by any imaginable technology? Probably not. But what if the ischemic interval lasts for an hour — or two hours, or a day? We simply don't know where to draw the line between one patient who is potentially viable, and another who is not.
http://www.alcor.org/problems.html

Now Becker is actually answering those questions and drawing that line.

"Half the time in cardiac arrest, we get the heart going again, blood pressure is good, everything is going along," says Dr. Terry Vanden Hoek, director of the Emergency Resuscitation Center at the University of Chicago, "and within a few hours everything crashes and the patient is dead." It took some time, though, for basic research to supply an explanation. Neumar, working with rats, simulates cardiac arrest and resuscitation, and then examines the neurons at intervals afterward. Up to 24 hours later they appear normal, but then in the next 24 hours, something kicks in and they begin to deteriorate.

What we found when we studied oxygen deprivation in cells astounded us,” explained Becker. “When cells are deprived of oxygen for an hour there is only 4% cell death. After four hours, cell death is only around 16%. Both of these numbers are low. The amazing thing was once we re-introduced oxygen to the cells they died off rapidly to almost 60% cell death. This re-oxygenation injury we termed reperfusion injury. We concluded that the re-introduction of oxygen must be handled carefully for the majority of cells to survive.
http://www.uphs.upenn.edu/news/News_Rel ... enter.html

Becker has taken the heart attack survival rate from from 15% to 80%
http://www.newsweek.com/id/35045

How many humans has Alcor revived?

[MirariNefas]

I work in a lab which developed a drug undergoing clinical trials, which is meant to decrease the severity of hypoxia and reperfusion injury. This drug was developed based on research into hibernating animals.

The vast majority of research into hibernation and therapeutic hypothermia is not useful to a company like Alcor. They are using vitirification, and their process would kill you if you weren't already dead. It's like the difference between going into the refrigerator for a little while, and being pickled and stuffed in the freezer for decades.

[Skipjack]

My ref about Becker induces 33 degreeC Mild Hypothemia for the purpose of preventing the self-destruction of cells after oxygen is reintroduced. Its specifically for heart attacks and I speculate also drowning, and not suitale for hemorrhaging patients.

It was 32 degress C in my case.
What can I say? It worked! And pretty well too. I had no noticeable brain damage (though I swear that I can not quite concentrate as well anymore as I used to) and my heart is actually doing quite well too. Muscles are fine. Two weeks after the attack I felt rather fit again. That even though I was in cardiac arrest and clinically dead.

[djolds1]

What can I say? It worked! And pretty well too. I had no noticeable brain damage (though I swear that I can not quite concentrate as well anymore as I used to)

Try Ritalin/Adderall and/or Aricept.

and my heart is actually doing quite well too.

Good.

That even though I was in cardiac arrest and clinically dead.

Complete cardio-pulmonary failure and clinical death for 2 minutes when I was 3.5 years old. No cooling involved, minor neurological annoyances and some other minor deficits.

[kurt9]

Duh! This have been obvious to us since the mid 80's when the guys I know at Alcor did their dog experiments.

Theoretically yeah. Animal experiments, fine.
But Duh? How then is it that hospitals the world around currently have it so wrong?

With this realization came another: that standard emergency-room procedure has it exactly backward. When someone collapses on the street of cardiac arrest, if he's lucky he will receive immediate CPR, maintaining circulation until he can be revived in the hospital. But the rest will have gone 10 or 15 minutes or more without a heartbeat by the time they reach the emergency department. And then what happens? "We give them oxygen," Becker says. "We jolt the heart with the paddles, we Blood-starved heart muscle is suddenly flooded with oxygen, precisely the situation that leads to cell death. Instead, Becker says, we should aim to reduce oxygen uptake, slow metabolism and adjust the blood chemistry for gradual and safe reperfusion.
http://www.newsweek.com/id/35045

So from Alcor

Another project was a study of cat brains. These were perfused and frozen under a variety of conditions, in an effort to assess problems that would occur in human suspensions. Examinations were made at the macroscopic, histological (cellular) and ultrastructural levels. Results showed that, while fine structure clearly was being preserved, the preservation was not perfect. Basic questions remained unanswered, such as whether identity-critical information would be adequately retained in frozen brain tissue. (These questions are still unanswered and await better understanding of how memories are stored.)
http://www.alcor.org/Library/html/researchhistory.html

Inability to Verify Results
Suppose a patient experiences 30 minutes of warm ischemia (lack of blood flow at near-normal body temperature) after legal death occurs. Will this downtime create damage that is irreversible by any imaginable technology? Probably not. But what if the ischemic interval lasts for an hour — or two hours, or a day? We simply don't know where to draw the line between one patient who is potentially viable, and another who is not.
http://www.alcor.org/problems.html

Now Becker is actually answering those questions and drawing that line.

"Half the time in cardiac arrest, we get the heart going again, blood pressure is good, everything is going along," says Dr. Terry Vanden Hoek, director of the Emergency Resuscitation Center at the University of Chicago, "and within a few hours everything crashes and the patient is dead." It took some time, though, for basic research to supply an explanation. Neumar, working with rats, simulates cardiac arrest and resuscitation, and then examines the neurons at intervals afterward. Up to 24 hours later they appear normal, but then in the next 24 hours, something kicks in and they begin to deteriorate.

What we found when we studied oxygen deprivation in cells astounded us,” explained Becker. “When cells are deprived of oxygen for an hour there is only 4% cell death. After four hours, cell death is only around 16%. Both of these numbers are low. The amazing thing was once we re-introduced oxygen to the cells they died off rapidly to almost 60% cell death. This re-oxygenation injury we termed reperfusion injury. We concluded that the re-introduction of oxygen must be handled carefully for the majority of cells to survive.
http://www.uphs.upenn.edu/news/News_Rel ... enter.html

Becker has taken the heart attack survival rate from from 15% to 80%
http://www.newsweek.com/id/35045

How many humans has Alcor revived?

We know that neurostructure breaks down quickly following cessation of metabolism. Obviously it survives longer than an hour, but we know from our own EM analysis that it breakdown in less than 12 hours and probably within 6 hours. That's why the vitrification process has to be started quickly once the patient deanimates. There are legal and institutional barriers that often prevent immediate vitrification of many Alcor Patients.

My point was that this recent "hypothermia" research is simply confirmation of work that Alcor did in the mid 80's. That not only does the neuro-structure survive following cessation of electrical activity, but that the injury caused by Oxygen deprivation is due to re perfusion that occurs when the Oxygen is restored to the brain. Indeed, we used this precise term, re-perfusion injury, to decribe the injury mechanism when talking about it in the late 80's (Mike Darwin coined this term at the time). So, I stand by my ealier comment that Alcor actually pioneered this work in the mid 80's, even though they never submitted papers for peer-review (which is probably the reason why you never heard of it).

The vitrification process is optimized to preserve neurostructure, but causes damage to the rest of the body. The reason has to do with how the "therapeutic window" of the cryo-protectant agents used vary depending on tissues and that the concentration of cryo-protectant that is optimized for preserving brain structure causes damage to other tissues. Since the seat of human conscious is the brain, this is the part of the body that must be preserved. Some kind of regeneration based on stem-cell, synthetic biology, or bionanotechnology will be necessary to reconstruct and reanimate the patient. Since the aging process is the largest cause of death at this time (and the reason for cryopreservation) there is no point to reanimating anyone even if we could because we still do not have a cure for aging (SENS is the most likely prospect for this, but is still several decades away).

BTW, the snarky tone of your comments is uncalled for.

[kurt9]

I work in a lab which developed a drug undergoing clinical trials, which is meant to decrease the severity of hypoxia and reperfusion injury. This drug was developed based on research into hibernating animals.

The vast majority of research into hibernation and therapeutic hypothermia is not useful to a company like Alcor. They are using vitrification, and their process would kill you if you weren't already dead.

This is very true.

Vitrification process is optimized to preserve the neuro-structure of the brain as free from damage as possible. This requires a certain concentration of cryo-protectant (essentially biological anti-freeze solution) to prevent the freezes or chilling damage cause by the cooling process itself. The problem is that the cryo-protectant solution has a narrow therapeutic window. Too little and the freezing/cooling damage occurs. Too much and the cryo-protectant itself is toxic. This therapeutic window varies depending on tissue type. So, the amount of cryo-protectant that is optimized for neuro-preservation damages other tissues in the body. This is the reason why whole-body vitrification (e.g. SF-style suspended animation) is probably impossible.

Reanimation of suspension patients will require a regeneration technology. This technology will likely be based on some kind of stem-cell based regeneration combined with synthetic biology. Although there are no guarantees in this life or any other, it is plausible that such a technology can be developed, say by 2100 or so. After all, biological regeneration and synthetic biology are hot fields now. I have no difficulty in envisioning such a regenerative technology will be commonplace by 2100.

They relevancy of this hibernation work to us is that it demonstrates that "death" does not automatically occur when brain electrical activity ceases. That as long as the neuro-structure of the brain remains intact, you are still alive, even if you are not active. This strengthens the case for cryonics.

[MirariNefas]

This requires a certain concentration of cryo-protectant (essentially biological anti-freeze solution) to prevent the freezes or chilling damage cause by the cooling process itself. The problem is that the cryo-protectant solution has a narrow therapeutic window. Too little and the freezing/cooling damage occurs. Too much and the cryo-protectant itself is toxic.

The vitrification process is doing a little more than providing biological antifreeze. There are biological antifreezes used by many organisms without harm, even in their brains. This is not enough for Alcor, and is part of where they diverge from having any therapeutic potential. The problem is, not all chemical reactions stop once you reach 0 C, and naturally occuring biological antifreezes don't depress the freezing point too much below (I forget the current limit, but I'll guess it's around -10 C). Many processes may stop at this temperature, others will be greatly slowed, and for therapeutic purposes, this is enough. If we could bring people down to 5 C, we could keep them under for enough time to manage whatever surgery or other trick we're trying.

Cryonics, on the other hand, can't tolerate even very slow biochemical breakdowns, because they need to preserve you until 2100+. So they have to load you up with enough chemicals that it is essentially toxic even to the brain.

Reanimation of suspension patients will require a regeneration technology.

Yes. A cloned body is a good start.

This technology will likely be based on some kind of stem-cell based regeneration combined with synthetic biology.

I fail to see how synthetic biology would be useful, but okay.

What I'd like to know is how they're planning on reviving the brain. I get the rest, yes, replacement tissues and everything. But the last time I checked (it was a few years ago and I didn't know as much then, I must admit) it looked like their only plan was magic nanites.

They relevancy of this hibernation work to us is that it demonstrates that "death" does not automatically occur when brain electrical activity ceases. That as long as the neuro-structure of the brain remains intact, you are still alive, even if you are not active.

Ah. Yes, this has been known for some time.

Did you know that electrical activity in the brain of the hibernating ground squirrel completely ceases? They don't dream. In fact, the dendrites connecting nerve cells retract to avoid damage. And yet, they're capable of waking up within a matter of hours, and as I understand it they don't seem to display any substantial memory loss. I wish we knew how to replicate that particular feat.