19 replies to this topic

[DukeNukem]

Was torn about where to put this topic, but cryonics is as good as any.

I think we're on the cusp of a paradigm shift in health care, especially urgent care and traumatic cases. And one that will also have huge ramification for cryonics.

Low doses of the toxic gas responsible for the unpleasant odor of rotten eggs [hydrogen sulfide] can safely and reversibly depress both metabolism and aspects of cardiovascular function in mice, producing a suspended-animation-like state.
http://www.scienceda...80325083254.htm

This works through a very telling mechanism: It suppresses all oxidation processes within the metabolism. In essence, practically all permanent ( <---- key word here!) death is the result of reduced oxygen within our cells, leading to a cascade of toxic last-gasp chemical reactions that result in permanent structural cellular damage. My first-thought analogy is that of a dying star, which is nearly devoid of hydrogen and helium (the preferred fuels for fusion), and then the star quickly begins burning through heavier elements, until it reaches lead, a non-fusion-able waste product, at which point the star permanently dies (or violently implodes/explodes--a supernova).

Anyway, suspended animation is achievable if all oxygen can be quickly eliminated from a biological entity, such that this cascade cannot take place. The entity is essentially dead (non-functioning), but restoration of oxygen can return it to life. This is the part that pertains to cryonics--people who've died need to have their remaining in-body oxygen neutralized as fast as possible!

It turns out that hibernating animals have evolved similar biological mechanisms. For example, a hibernating bear builds up a huge supply of body fat, which it burns through slowly during the winter months. Burning fat in this way requires very little oxygen, and therefore the bear survives at a very low metabolic rate, just as with the mice in the story I linked to.

The key is oxygen -- we have about 10 minutes of oxygen stored in our blood and our tissues. If this oxygen could be very quickly evacuated or rendered inert, we are in effect dead, but revive-able. And this is what we can now do in lower life forms using hydrogen sulfide.

This, btw, has an interesting consequence relating to CPR: We should NOT breath oxygen into a heart attack victim. This oxygen merely adds to the potential damage that can and will be done if the victim is not revived by the 8-10 minute mark. And, this also explains why people who fall into ice water or get trapped under an avalanche, can survive for up to an hour of not breathing -- the hypothermia dramatically reduces the damaging cascade of oxygen-based metabolic reactions.

I have a lot more thoughts on this, but I'll stop here.

[bgwowk]

It's a bit of an oversimplification to blame ischemic injury so entirely on oxygen. As an illustration, if you don't treat someone with a stopped heart and just leave them untouched, the brain will exhaust its oxygen stores in less than a minute. Yet damage will still progress in the minutes and hours that follow. Clinically, people who receive CPR, getting some oxygen to the brain before cardiac resuscitation, will do better than people who don't receive CPR before their heart is restarted. The main clinical insight that has come from the role of oxygen in reperfusion injury is that it appears to be better to ventilate patients with air (21% oxygen) rather than pure oxygen after cardiac resuscitation. I'm not aware of any evidence that not providing oxygen at all (such as by blocking the airway or ventilating with an inert gas) is beneficial for CPR.

Hypothermia improves survivability of ischemia because it slows all damage mechanisms, whether caused by oxygen or not.

[DukeNukem]

Clinically, people who receive CPR, getting some oxygen to the brain before cardiac resuscitation, will do better than people who don't receive CPR before their heart is restarted.

What makes you think this?

[bgwowk]

Clinically, people who receive CPR, getting some oxygen to the brain before cardiac resuscitation, will do better than people who don't receive CPR before their heart is restarted.

What makes you think this?

There have been instances of people surviving an hour of CPR at normal body temperature before their heart could be restarted. Nobody has survived an hour of normothermic cardiac arrest with no CPR. That it is better for the brain to do CPR rather than not do CPR is why CPR is done.

[Sillewater]

Peter Ward: Earth's mass extinctions



He talks about this towards the end of the talk.

Edited by Sillewater, 17 January 2010 - 05:06 AM.

[Loot Perish]

[DukeNukem]

Clinically, people who receive CPR, getting some oxygen to the brain before cardiac resuscitation, will do better than people who don't receive CPR before their heart is restarted.

What makes you think this?

There have been instances of people surviving an hour of CPR at normal body temperature before their heart could be restarted. Nobody has survived an hour of normothermic cardiac arrest with no CPR. That it is better for the brain to do CPR rather than not do CPR is why CPR is done.

Having done more research on this yesterday, I discovered that in Arizona and in Seattle, emergency medical protocol has been modified so that CPR no longer involves a respiratory aspect -- in fact, they purposely avoid giving air/oxygen. Heart attack survival rates have dramatically improved by just applying pumping pressure to the heart (to keep blood flow moving through the body).

For example: http://www.callandpump.org/pdf/a1.pdf

This strongly supports my speculation that oxygen becomes deadly during certain periods when in short supply. Weakly effective respiratory methods such as CPR simply cannot elevate systemic oxygen to life saving levels, and therefore no respiratory measure should be attempted, because the slight oxygen that is added to the blood merely leads to more oxidative damage to cellular structures.

This puzzle falls together nicely if you pay close attention to my original post, and the implications behind it.

[DukeNukem]

It really seems to me like the cryonics companies should be looking very closely into this, because if they could reduce oxidative damage by quickly removing oxygen from a body (replacing it with a non-oxidative gas), it would greatly reduce damage. Freezing the body helps to an extent, but is a very crude method. The same effect, if not better, could possibly be developed that doesn't require bulking cooling equipment, and therefore by far more convenient and portable.

[Mind]

Or cooling + H2S could be superior for reducing damage immediately after legal death, than either one by itself.

[Athanasios]

Having done more research on this yesterday, I discovered that in Arizona and in Seattle, emergency medical protocol has been modified so that CPR no longer involves a respiratory aspect -- in fact, they purposely avoid giving air/oxygen. Heart attack survival rates have dramatically improved by just applying pumping pressure to the heart (to keep blood flow moving through the body).

Just a note. I think the most updated recommendations for EMTs, nationwide in 2010, have stopped the breathing into the victim aspect of CPR and are now switching to essentially chest compression only, which still allows passive breathing. The ALCOR trainers also taught this in the first responder course that I attended.

If you want to do some googling/reading of the passive breathing effect, search 'Passive Oxygen Insufflation'. Upon looking into it further myself, there is still a discrepancy between a shockable and non-shockable rythyms. Much of the beneficial effect of no assisted ventilation seems to be due to the shockable rhythm group.

I also wonder how relevant this will be in a cryonics response situation. If the patient is attended to that quickly, it is likely that anti-ischemia/clotting/etc meds and cool down would also be started immediately (with a viable IV line or IO port available).

BTW, thanks for bringing this up Duke.

[bgwowk]

It really seems to me like the cryonics companies should be looking very closely into this, because if they could reduce oxidative damage by quickly removing oxygen from a body (replacing it with a non-oxidative gas), it would greatly reduce damage. Freezing the body helps to an extent, but is a very crude method. The same effect, if not better, could possibly be developed that doesn't require bulking cooling equipment, and therefore by far more convenient and portable.

The extrapolation of a very specific experiment in mice to a conclusion that removing oxygen from humans results in suspended animation is not warranted. Anoxia, whether by metabolic exhaustion of available oxygen stores during ischemia, or reducing partial pressure of oxygen in lungs to zero by breathing an inert gas, does not result in any kind of stasis. It results in a cascade of damage that within minutes at normal body temperature will make recovery by present medical technology impossible.

To cnorwood:

Eliminating the assisted ventilation step of CPR is based on the discovery the chest compressions themselves cause air movement in and out of lungs. It is not based on an avoidance of getting oxygen to the patient. The first step of CPR is still to check the patient for a clear airway, without which CPR is pointless. The purpose of CPR is to get oxygenated blood flowing through the brain and heart to keep them viable. The proof of utility of keeping the brain oxygenated during cardiac arrest is that patients who get CPR survive better than patients who don't. I guarantee that removing all oxygen from lungs during CPR would make that benefit go away.

To Mind:

The hypometabolic response of mice to H2S is not universal. There have been failures reproducing it in larger animals

http://www.depressed...olism-in-sheep/

http://www.nature.co...nbt0109-13.html

Skeptics wonder if H2S will ever achieve its clinical goals. A recent study by Andrew Redington, division head in cardiology at the University of Toronto's Hospital for Sick Children, could not replicate Roth's mouse findings in piglets, prompting speculation that H2S's metabolism-slowing effect might not be attainable in large animals, including humans. Sam Tisherman, a surgeon at the University of Pittsburgh Medical Center, who investigates suspended animation in pigs, concedes that "questions surrounding efficacy in large animals still need to be answered."

CI did not obtain benefit in hypothermic rat brain tissue slices

http://www.cryonics..../july05/h2s.htm

That's not to say that H2S won't have uses for ameliorating ischemia/reperfusion injury, including cerebral ischemia reperfusion. The utility is just not as obvious as once thought, and much more research needs to be done. It's not a panacea for suspended animation in humans. It's more accurately viewed as a pharmaceutical with some emerging specific applications.

[DukeNukem]

It really appears that NOT doing CPR with the "giving breaths" technique, as taught for decades, is the best way: just focus on chest compressions:

With less emphasis on cardiopulmonary resuscitation (CPR) and changing our focus to CCC (continuous chest compressions), Montgomery said, survival rates have started sky rocketing.

“From decades of 1 to 2 percent successful resuscitation rates, we are in the high teens of percentage of survivability. That is based on the history we have now of four years of accurate record keeping,” Montgomery said.
http://www.azchiefs....mp;pressid=1037

There's a lot more about this online. In fact, I found out that a new book by Dr. Sanjay Gupta, Cheating Death, has a full chapter on this, and he talks about how, even with outstanding improve survival rates by NOT giving patients oxygen, the vast majority of the medical community sticks with standard CPR. Like all old school beliefs and systems, this one is not going to be replaced easily, even if it means 10's of 1000's of people will die in the meantime.

[DukeNukem]

Bottom-line: If you ever have a need to do CPR...DON'T!!!! Your chances of saving that person are minuscule at best with this outdated technique. Instead, do CCC--continuous chest compressions--until professional help arrives. And if you have bystander help, make the person as cold as possible. For example, drag them to a meat cooler asap, or put ice packs from a nearby gas station all around their body. All the while, ignore giving breaths and focus on compressions.

[bgwowk]

Bottom-line: If you ever have a need to do CPR...DON'T!!!! Your chances of saving that person are minuscule at best with this outdated technique. Instead, do CCC--continuous chest compressions--until professional help arrives. And if you have bystander help, make the person as cold as possible. For example, drag them to a meat cooler asap, or put ice packs from a nearby gas station all around their body. All the while, ignore giving breaths and focus on compressions.

Focus on chest compressions rather than pausing for breaths, absolutely. The purpose of this is to get oxygen to the brain more effectively than old-style CPR. It was discovered that compressions themselves ventilate the lungs, and the drop in brain blood pressure and oxygenation that occurs when compressions are paused for breaths is why old-style CPR wasn't as good the new CCC-CPR. CPR is all about getting life-sustaining amounts of oxygen to the brain. CCC-CPR is better because it does a better job of it.

The first priorities are continuous chest compressions and early defibrillation. Ice packs might be applied to high heat exchange areas like the neck only if it is possible without any interruption of chest compressions. Cooling is generally considered to be part of post-resuscitation care. I think cooling someone meaningfully while concentrating on continuously delivering 100 compressions per minute and ensuring EMS is contacted would be very difficult.

None of this is to say that too much of a good thing can't be bad. That's why some resuscitation experts have been recommending that initial post-resuscitation ventilation be with air rather than 100% O2.

Edited by bgwowk, 18 January 2010 - 05:24 AM.

[DukeNukem]

There is no evidence that the common practice of giving patients oxygen to inhale during a heart attack is beneficial, according to a new Cochrane Systematic Review. Until further research is carried out, the researchers say the possibility that giving oxygen may actually increase a patient's risk of dying cannot be ruled out.

http://www.scienceda...00615191651.htm

[JonesGuy]

I think the search term 'pre-ischemic conditioning' is the best term to use to show why CPR is so useful.

Periods of low oxygen are much less damaging than periods of no oxygen. Any flow of blood through the tissue will prevent anoxia (hopefully). As well, good bouts of CRP will allows some tissues to benefit from post-ischemic conditioning, which is a technique where 'pulses' of oxygenated blood are introduced into an ischemic area.

[xlifex]

Is there any meaningful research that tries to answer the question whether the benefits of continuous compression CPR is due to reduced oxygen (100% oxygen vs room air) or whether these benefits simply reflect improved cardiac output during chest compressions because there are no interruptions for ventilations. This is an important difference as far as the role of oxygen in resuscitation is concerned.

Edited by xlifex, 16 June 2010 - 08:15 PM.

[PWAIN]

This thread seems to deal with the same idea:

http://www.imminst.o...showtopic=40430

From that thread:

Consider someone who has just died of a heart attack. His organs are intact, he hasn't lost blood. All that's happened is his heart has stopped beating—the definition of "clinical death"—and his brain has shut down to conserve oxygen. But what has actually died?

As recently as 1993, when Dr. Sherwin Nuland wrote the best seller "How We Die," the conventional answer was that it was his cells that had died. The patient couldn't be revived because the tissues of his brain and heart had suffered irreversible damage from lack of oxygen. This process was understood to begin after just four or five minutes. If the patient doesn't receive cardiopulmonary resuscitation within that time, and if his heart can't be restarted soon thereafter, he is unlikely to recover. That dogma went unquestioned until researchers actually looked at oxygen-starved heart cells under a microscope. What they saw amazed them, according to Dr. Lance Becker, an authority on emergency medicine at the University of Pennsylvania. "After one hour," he says, "we couldn't see evidence the cells had died. We thought we'd done something wrong." In fact, cells cut off from their blood supply died only hours later.

But if the cells are still alive, why can't doctors revive someone who has been dead for an hour? Because once the cells have been without oxygen for more than five minutes, they die when their oxygen supply is resumed. It was that "astounding" discovery, Becker says, that led him to his post as the director of Penn's Center for Resuscitation Science, a newly created research institute operating on one of medicine's newest frontiers: treating the dead.

Biologists are still grappling with the implications of this new view of cell death—not passive extinguishment, like a candle flickering out when you cover it with a glass, but an active biochemical event triggered by "reperfusion," the resumption of oxygen supply. The research takes them deep into the machinery of the cell, to the tiny membrane-enclosed structures known as mitochondria where cellular fuel is oxidized to provide energy. Mitochondria control the process known as apoptosis, the programmed death of abnormal cells that is the body's primary defense against cancer. "It looks to us," says Becker, "as if the cellular surveillance mechanism cannot tell the difference between a cancer cell and a cell being reperfused with oxygen. Something throws the switch that makes the cell die."

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 pump in epinephrine to force it to beat, so it's taking up more oxygen." 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.

Researchers are still working out how best to do this. A study at four hospitals, published last year by the University of California, showed a remarkable rate of success in treating sudden cardiac arrest with an approach that involved, among other things, a "cardioplegic" blood infusion to keep the heart in a state of suspended animation. Patients were put on a heart-lung bypass machine to maintain circulation to the brain until the heart could be safely restarted. The study involved just 34 patients, but 80 percent of them were discharged from the hospital alive. In one study of traditional methods, the figure was about 15 percent.

Becker also endorses hypothermia—lowering body temperature from 37 to 33 degrees Celsius—which appears to slow the chemical reactions touched off by reperfusion. He has developed an injectable slurry of salt and ice to cool the blood quickly that he hopes to make part of the standard emergency-response kit. "In an emergency department, you work like mad for half an hour on someone whose heart stopped, and finally someone says, 'I don't think we're going to get this guy back,' and then you just stop," Becker says. The body on the cart is dead, but its trillions of cells are all still alive. Becker wants to resolve that paradox in favor of life.



I am getting more convinced that this is the key to a lot of the cell death issues and that cooling is possibly mainly effective because of this.

[CryoBurger]

I discovered that in Arizona and in Seattle, emergency medical protocol has been modified so that CPR no longer involves a respiratory aspect -- in fact, they purposely avoid giving air/oxygen

That's odd. My mom just died on Christmas, in phoenix Arizona, and when she collapsed, the 911 operator told us to breathe in her mouth while pushing. When the Chandler Regional Medical Center EMT's arrived, they administered oxygen, or at least that mask thing they squeeze with their hand. I have actually heard the opposite from an ER friend - that they actually prefer to avoid doing CPR completely because it tends to break the ribs when done properly, and can pierce the heart or other internal organs. But that's another topic.

As a side note, just pushing didn't do anything for her. We actually brought her back to life by breathing into her. She responded by coughing and "waking up" from being dead. Nothing was working until my step father did the inhale. She regained a 45 pulse which later slowed to a stop.

They stopped trying after 45 minutes. Also odd to hear that some have survived after an hour ... guess it depends on the causes.

-P-

Edited by CryoBurger, 17 June 2010 - 10:53 PM.

[JLL]

I think the low oxygen + low metabolism approach is going to yield some interesting discoveries in the future. Of course treating patients is the first step, but this sure seems like it could improve cryonics too.