Do neurons actually die within 5 minutes of anoxia?

[Ruslan_Sharipov]

Anoxia is a condition in which there is no delivery of oxygen to tissues of the body. Generally it occurs in cardiac arrest or upon termination of access of air into the lungs. Different tissues have different degrees of resistance to anoxia. It is thought that the least stable are neurons, the cells of the nervous tissue. It is believed that neurons die within 5 minutes of anoxia. Is this true? I have found no indication to direct evidence animal experiments that support this opinion. However I have discovered some facts which indirectly suggest that this view may be erroneous. I propose to discuss these facts.

1. The world record by Tom Sietas. German diver Tom Sietas, competing in Changsha, China have set a new breath-holding world record of 22 minutes and 22 seconds. This was done in front of TV cameras of Chinese television.

2. The event of Fabrice Muamba, a professional footballer from Bolton Wanderers, England. His heart stopped right during the match and did not beat for 78 minutes.

3. Statistical data by American scientists published in their paper

Hallstrom A, Cobb L, Johnson E, Copass M., Cardiopulmonary resuscitation by chest compression alone or with mouth-to-mouth ventilation, New Engl. J. of Med., 2000, Vol. 342, No. 21, https://depts.washington.edu/respcare/public/hmc_files/journal_club/articles/20110321/CPR_by_chest_compressions_alone_or_with_mouth-to-mouth.pdf.

Analyzing emergency calls because of cardiac arrest, they write that the number of survivors among patients who received only chest compressions higher than among those who received chest compressions and mouth-to-mouth ventilation. They also mention some experimental studies. Characterizing these studies, they write verbatim: "In experimental studies, chest compression alone is associated with survival rates similar to those with chest compression plus mouth-to-mouth ventilation".

 

[Evo]

I don't think you understand what they said in the link you supplied. You failed to state what you agree with or disagree with in the study. If you disagree, then you need to furnish a study that shows that additional ventilation past the first few minutes is not needed. You have not done that.

During the almost seven years of the trial, substantial laboratory work has been done on the issue of ventilation during CPR. This is well summarized in a special report from the Ventilation Working Group of the Basic Life Support and Pediatric Life Support subcommittees of the American Heart Association.12 The committee concluded that “it seems possible that mouth-to-mouth ventilation is not needed during the first few minutes of sudden witnessed circulatory arrest . . . and may, in fact, have . . . potential disadvantages, including gastric insufflation and less cycle time spent on effective chest compressions.” The committee did not recommend that the guidelines be changed, largely out of concern for the usefulness of ventilation for arrests due to primary respiratory causes. Given the committee's appraisal and the results of this trial, we believe chest-compression CPR may be applicable to the more general setting of bystander-initiated CPR.

Also, the breath holding contest is suspect and the soccer player was in an ambulance being treated within 6 minutes, he didn't go without ventilation if that's what you expect us to believe.

 

[Ryan_m_b]

World records are not a good standard to use when trying to investigate biology. By definition people who hold world records are outliers, either through intense training or innate biology or both. Also people who can hold their breath for incredibly long periods of time take advantage of certain tricks like doing the feat in a freezing cold tank of water which causes blood flow to the extremities to reduce, meditation techniques to slow down heart rate and even breathing of pure oxygen before the attempt.

Regarding the footballer in question I can't find a source that goes into detail of what medical procedures he underwent but he wouldn't have just received hand's only CPR for the whole 78 minutes. More likely the had some form of artificial respiration, probably a BVM.

The reason why hands only CPR is advised for members of the public is that it is easier and in the first few minutes mouth-to-mouth is not needed. Furthermore MTM can be done incorrectly harming the patient. Remember that CPR by a member of the public is solely done to give the patient a chance before a trained professional gets there and can do something better.

 

[.Scott]

Excluding cases where the victim becomes very chilled (ex, falls through the ice), someone who has suffered a heart attack and is left untreated for 5 minutes has only a miniscule chance of survival. And should they survive, their recovery will be very limited and they have no chance of returning to work - the main problem being with damage to the central nervous system.

I do not know if this damage is actual cell death.

In the article below, neurons were deprived for over twice this time before permanent damage was observed. However, only one death mechanism (Calcium rise leading to membrane depolarization) was monitored.
This article: https://stroke.ahajournals.org/content/29/1/196.full

In an intact human body, there is other chemistry going on - and I seem to remember other mechanisms related to the overall blood chemistry that are important.

Here is a study that supports your assertion that COCPR (compression-only CPR) can be more effective. The specific situation where COCPR showed its greatest merit was in "bystander witnessed" cases, where the victim was seen by the rescuer falling unconscious (as opposed to being found unconscious). For the first few minutes after the heart stops, the problem is not a lack of oxygenated blood, but a lack of circulation to allow that blood to perfuse.

http://jama.jamanetwork.com/article.aspx?articleid=186668

One of the reasons that COCPR is promoted is that it is simpler and, because it lacks the "yuck" factor, more people are likely to use it. So one may suppose that people using COCPR may begin compressions a bit earlier.
More importantly, if the compressions are not being performed well (and it takes a lot of effort to keep them going strong), not breaking after every 30 strokes may be just what the victim needs for adequate perfusion.

I should add that the American Heart Association recommendations for CPR are very thoroughly reviewed in five year cycles. I looked in detail at their review process for 2005 (ECC2005, ILCOR) and it is very impressive in the way in assembles the latest studies in determining exactly what should be provide in the way of layman and professional instruction.

 

[.Scott]

Here's an interesting article that says that having the rescuer rest for 10 seconds after every 100 compressions (1 minutes worth) results in higher quality compressions.

http://www.sciencedirect.com/science/article/pii/S0300957213000981

It's interesting because I would guess that in most cases in that Arizona study a portable AED would become available within that minute.

 

[berkeman]

Here's an interesting article that says that having the rescuer rest for 10 seconds after every 100 compressions (1 minutes worth) results in higher quality compressions.

http://www.sciencedirect.com/science/article/pii/S0300957213000981

It's interesting because I would guess that in most cases in that Arizona study a portable AED would become available within that minute.

It's better for the patient if we do CPR in a team fashion. The only time you rest is when someone else on the team is doing compressions. We trade positions (compressions, breaths) about every 5 cycles (about every 2 minutes).

 

[.Scott]

It's better for the patient if we do CPR in a team fashion. The only time you rest is when someone else on the team is doing compressions. We trade positions (compressions, breaths) about every 5 cycles (about every 2 minutes).

Working in teams has always been part of the instruction for professional rescuers.

With the new CPR requirements (depth and frequency) in ECC2010, I really wonder why they haven't suggested that, after someone has been dispatched for the 911 and the AED, the next one isn't recruited to assist with the compressions. I'm guessing that it's just too much to expect of a lay rescuer.

 

[Ruslan_Sharipov]

Also, the breath holding contest is suspect...

The contest in Changsha, China (May 30, 2012) is not unique. You can see the list of breath holding world records in Wikipedia.

...the main problem being with damage to the central nervous system. I do not know if this damage is actual cell death.

I support your doubt about cell death of neurons. It is known that a special bandage (tourniquet) is applied to a limb in order to stop arterial bleeding. The tourniquet can be applied during 1-2 hours. So limb cells can survive in anoxia while the tourniquet is applied. I do not believe that neurons are strongly different from other cells. My conjecture is that neurons do not die within 5 minutes of anoxia, they just stop their specific electrical activity. There must be some tools (some chemical substances and/or electrical stimulating devices) that can force neurons to restart their electrical activity if anoxia is removed within 1-2 hours or so.

In the article below, neurons were deprived for over twice this time before permanent damage was observed. However, only one death mechanism (Calcium rise leading to membrane depolarization) was monitored. This article: https://stroke.ahajournals.org/content/29/1/196.full

Are you sure that membrane depolarization is equivalent to cell death? If this is certainly so and if this is the primary death mechanism, then there must be some chemical substances (conservants) that capture Ca²⁺ ions thus preventing neuron death.

Probably brain capillars are thrombosed within 5 minutes of circulatory arrest. If so, it is clear why the compression only CPR is effective when it is followed by transportation to a hospital along with professional reanimation procedures on the way there.

 

[.Scott]

Are you sure that membrane depolarization is equivalent to cell death? If this is certainly so and if this is the primary death mechanism, then there must be some chemical substances (conservants) that capture Ca²⁺ ions thus preventing neuron death.

According to the article:

When O2/glucose deprivation exceeded 13 to 15 minutes, both membrane depolarization and [Ca2+]i rise became irreversible.

I would think that in the case of a neuron, irreversible membrane depolarization would be tantamount to death since it would no longer be capable of functioning as a neuron.

 

[Ruslan_Sharipov]

According to the article: "When O₂/glucose deprivation exceeded 13 to 15 minutes, both membrane depolarization and [Ca²⁺]i rise became irreversible".

Well, but looking through the article, I did not find any words saying that the authors continued their observations resuming O₂/glucose supply after 15 minutes of deprivation until the total death of neurons, i. e. until their cellular destruction, or maybe until their recovery. Moreover, the title of the article says "L-Type Ca²⁺ Channel Blockers Attenuate Electrical Changes and Ca²⁺ Rise...". The authors indicate two substances Nifedipine and Nimodipine that "significantly reduced either the membrane depolarization or the [Ca²⁺]i elevation". This means that negative changes in neurons can be controlled.

 

[Choppy]

I think there are a few issuess at play here.

First - how are you defining anoxia? In my background there is a difference between hypoxic (below normal levels of oxygen concentration) and anoxic (essentially zero oxygen concentration) cells. I suspect that you're confusing a more broad definition that would be applied to a tissue in the absence of breathing with a more specific definition that's restricted to the microscopic scale.

Second, in situations where the macroscopic processes of breathing ceases, or perhaps a torniquet is applied, the oxygen concentration in the cells of all tissues does not immediately drop to zero. I don't know exactly what the decay curve looks like, but I suspect that it depends strongly on the metabolism of the cell. Cells that are reasonably dormant will likely maintain their oxygen concentrations longer.

Third, cells are very complex things. In cancer biology, tumour cells quite often live in states of constant hypoxia because they have outgrown the framework of their microvasculature. But, they shift towards anaerobic respiration and survive. I don't know a lot about neurons specifically, but I suspect you will have a range of reactions once the oxygen supply is cut off. Some of the more fickle ones may die pretty quickly - whether by anoxic necrosis, or some sort of hypoxia-induced apoptosis, or apoptosis induced by some other phenomenon such as a buildup of carbon dioxide. Others may shift their metabolism similar to how cancer cells work. In time, of course, they will all die.

Fourth, I don't think there is any shortage of data on anoxic brain injury. My wife worked in brain injury rehabilitation for several years and many of her patients suffered such injuries.

 

[Ruslan_Sharipov]

Others may shift their metabolism similar to how cancer cells work.

I would like to add another reference. This is the book: Volpe J. J., Neurology of the newborn, 5th edition, Saunders and Elsevier, 2008, ISBN 978-1-4160-3995-2. On page 270 of this book we find the following text:

The crucial initial observation was that cultured hippocampal neurons obtained from the fetal rat were resistant to prolonged anoxia before synapse formation occurred in the cultures, but rthey were very sensitive to the same anoxic insult after synaptogenesis was well developped. ... However, when synaptic activity in these mature cultures was blocked by addition of high concentration of magnesium, no effects on the cultured neurons occurred.

This text means that, using a special therapy, neurons can be switched to some inactive state where they are resistant to prolonged anoxia just like cancer cells. Your idea is correct. I think it is applicable not only to special sorts of neurons, but to all neurons.