Mechanism of Oxygen Toxicity

[wetvet]

I am in the process of completing my advanced nitrox and decompression course. I have had a question about O2 tox since Nitrox 1, but it hasn't been answered yet, even in the advanced course. Likely it is irrelevant practically, but I would like to understand it. (Note, I have a medical background, so feel free to throw big words at me )

My confusion surrounds the mechanism of CNS toxicity of O2. 1) Is it caused by oxidizing neural tissue (or support structures), or 2) is it caused by interference with neural transmission (since O2 convulsions are supposedly of little medical importance if you dont drown), or 3) is it caused by free radical production and the havoc these little critters cause?

The reason for the question is that I am trying to understand the rationale behind the 24 hour Oxygen clock. I perfectly understand the ongassing and offgassing and compartments etc that explain Nitrogen. Oxygen makes less sense. If my exposure mounts with my depth and ppO2, but doesn't decrease with time (less than say 23 hours later), how does it reset to 0 one hour after that? Does it have to do with the bodys capacity to repair damage? Metabolism rates of neural tissues? Ability to mop up free radicals.....or (my suspicion) that it was arbitrarily set because it seemed to work.

Thanks for any info.....hope I didn't confuse anyone

Wetvet

 

[BigJetDriver]

In reference to the question about the mechanism of O2 toxicity, even the medical researchers who know the most about it admit that we do not know at present exactly how it happens.

I would refer you to works like "Diving and Subaquatic Medicine" by Edmonds, Pennefather, and Lowry. Another good choice would be "Diving Medicine" by Bove.

Perhaps Dr. Deco will have his finger on the pulse, so to speak, and will be able to refer us to more recent findings.

Doc?

 

[Dr Deco]

Dear Wetvet:

ROI Mechanisms

There is a generally agreement that oxygen-derived free radicals play some role in oxygen toxicity. Measurements with electron spin resonance spectroscopy have shown an increase in these in vivo with elevation of oxygen prior to increased electrical activity of the brain.

The mitochondrial pathways for the oxidation of metabolites will allow for the escape of some reactive oxygen intermediates (ROI). These are normally eliminated by the usually contingent of enzymes such as catalase, super oxide dismutase, etc. Fixed concentrations put an upward limit of the protection capability of these system.

The addition of long-term hyperoxygen can lead to the eventual interference in normal metabolism by these oxygen-derived intermediates. With return to normoxic conditions, the system will return to homeostasis.

Nitric Oxide

There is recent evidence that nitric oxide also plays a role by increasing brain blood flow. (Where in the vasculature does it not play a role?) Increased perfusion naturally means an greater influx of oxygen molecules.

CNS Clock

Similar to pulmonary oxygen toxicity, a CNS clock was developed. This allows the tracking (probably of ROI concentration and damage) over a certain period. For convenience, this is defined as a 24-hour period. I have not performed research in this CNS area and therefore am making a guess that there is a tacit assumption of sleep within the time frame. Thus, one can appear to dive for 23 hours and have the clock reset at 24 hours. That is not really how the system is to be used.

I really suspect that if you were to dive continuously for 24 hours per day for several days, taking catnaps between dives, the “accounting system” would break down. Implicit within it is a large “rest window.”

Dr Deco :doctor:

Please note the next class in Decompression Physiology :grad:
http://wrigley.usc.edu/hyperbaric/advdeco.htm

 

[Charlie99]

wetvet once bubbled...
The reason for the question is that I am trying to understand the rationale behind the 24 hour Oxygen clock

NOAA probably just used a 24 hour accumulative exposure for simplicity in manually tracking O2 exposure. Oceanic (and related Pelagic) computers use a 90 minute halftime for tracking the decay of O2 CNS effects. Suunto use a 60 minute halftime. I don't know the justification for their choices.

 

[wetvet]

Thanks for the info guys.....has cleared up some stuff (kinda).
Doc Deco: if the mechanism of Ox Tox appears to be primarily oxidation (the other factors seem to merely increase the availibility of oxygen to the neural tissues), it seems logical that someone would have recommended the use of Vitamin E as a prophylaxis. Ive never heard of this. Am I just out of the loop? It seems that a situation like this, where everyones succeptability is quite variable, that any safety factor would be utilised if possible.

Wetvet

 

[BigJetDriver]

Wetvet,

There are some, shall we say, more mature divers in the field of tech diving who do advocate the use of vitamin E, and other dietary supplements to help mitigate the increase in oxygen free-radicals in the hyperoxic diving environment. Tom Mount is one leader in the field who comes to mind.

To my knowledge there have been no definitive scientific studies of the efficacy of these supplements in the diving environment, but perhaps other readers might know of some.

I would caution, however, that while these supplements may help to mitigate the effects, they can in no way be described as preventative.

Doc, over to you.

 

[Dr Deco]

Dear wetvet:

Free Radical Scavengers

That is a good guess, and, yes, vitamin E has been recommended. This is certainly given by some practioners to patients during hyperbaric oxygen therapy, along with vitamin C. One can always try these if one wishes as they are OTC meds.

Super Oxide Dismutase

A bit more than a decade ago, advertisements for super oxide dismutase (SOD) tablets could be found in scuba magazines. This is a protein and is quite naturally hydrolyzed in the acidic gastric medium. Additionally it will mot penetrate the blood-brain barrier. Animal experiments have successfully loaded SOD into lipid vesicles and into brain cells. Convulsion levels were reduced. This is not practical for humans currently.

Carbon Dioxide

The only truly practical countermeasure has been the control of activity and the reduction of arterial carbon dioxide levels. Elevated CO2 will increase brain blood flow by autoregulation and is deadly when combined with elevated oxygen. O2 will overwhelm the free radical scavengers whose in vivo concentrations cannot yet be altered.

Dr Deco :doctor:

Readers, please note the next class in Decompression Physiology :grad:
http://wrigley.usc.edu/hyperbaric/advdeco.htm

 

[Charlie99]

wetvet once bubbled...
It seems that a situation like this, where everyones succeptability is quite variable, that any safety factor would be utilised if possible.

So far nobody has mentioned air breaks --- short periods on lower FO2 gas. This seems be the easiest way to add a huge safety factor when pushing limits with high FO2 deco gases.

IIRC the standard gas sequence in hyperbaric treatments such as USN treatment table 6 is 20 minutes O2, 5 minutes air. These air breaks generally prevent convulsions even while breathing O2 for over 60 minutes at ppO2 of 2.8ata.

I hear that wkpp (wkpp.org) uses similar air breaks (perhaps less than a 25 minute total cycle time) and routinely far exceeds the NOAA CNS limits.

 

[Saturation]

We discussed this at length a while back:

http://www.scubaboard.com/showthread.php?s=&threadid=23859&perpage=25&display=&pagenumber=2

There are extensive links, charts and graphs.