The Mechanism of Action of Nitric Oxide and Its Role in Healing Radiation Wounds

In this video, Dr. Treadwell shares insights into the role and mechanism of action of nitric oxide therapy for healing radiation wounds, which was used in a case series poster presentation (The Treatment of Wounds Occurring in Radiated Tissue with Nitric Oxide / Plasma Therapy) at SAWC Spring in National Harbor, Maryland, April 26-30, 2023.

Transcript:

Hello, this is Dr. Terry Treadwell. As many of you know, I'm the Medical Director for the Institute for Advanced Wound Care in Montgomery, Alabama.

Nitric oxide therapy is a very new therapy that we have for treatment of wounds. Nitric oxide, if you remember, is a normal compound that's in the body, a normal molecule. The gentleman who discovered nitric oxide was way back many years ago, his name was Dr. Joseph Priestley. He's also the gentleman who discovered oxygen, but nothing much could be done about it because nitric oxide is a molecule that contains one atom of nitrogen and one of oxygen.

When we talk about nitric oxide, everybody immediately thinks about nitrous oxide which is laughing gas, of course, but this is not the same thing. This is nitric oxide, which is one atom of nitrogen and one atom of oxygen. These two combined, the problem has been through all the years that this is a very unstable molecule, and has a half-life of about one to two seconds at the most.

As a result of that, even if we knew where to use it for treatment, it is not stable enough, long enough to actually cause some effect in tissue. Nitric oxide was found to be the major constituent that causes dilatation of small blood vessels. It is a substance that is made in the wall of blood vessels and causes a dilatation of those vessels.

We have clinically used nitric oxide indirectly by giving patients medication that would stimulate nitric oxide for production in the vessels themselves, in cause and effect. This actually was first recognized when people were making nitroglycerin many years ago. They found that in the manufactured nitroglycerin, the older gentlemen who were complaining of chest pain from vascular disease had no chest pain during the week, but on the weekends they would have angina.

As a result, studies showed that the nitroglycerin would dilate blood vessels. A gentleman in England went ahead and developed that into nitroglycerin tablets, and as you know, we still use that currently to treat patients who have angina or other types of vascular chest pain. It is also included in a number of other medications to stimulate the body's nitric oxide to see if we can dilate blood vessels. This has been very useful for heart disease, but we really haven't had the ability to treat anything else.

As time has gone on, we have learned more about nitric oxide and found that it has a number of other effects on the body and things that we need to know about. It is a very good antimicrobial. Nitric oxide will kill every microbe on the planet. That includes gram-negative, gram-positive, everything like that. There is no resistance to nitric oxide from the bacterial standpoint. It kills fungus very successfully. We've done work, and we'll talk a little bit about that as we go forward, that we can treat fungal infections such as toenail fungus. It also kills a number of viruses. We found that it does kill the virus that causes warts, and there are some studies that are being currently done to treat warts and things like that, to see if we can get the skin under control.

But again, treating skin problems and things along those lines, have been effective with the nitric oxide. What has made nitric oxide possible to be used clinically is a device that a gentleman from Russia developed. And what he did was, he found a way to produce the nitric oxide, and it also created a plasma energy wave. But it is an energy wave that is accomplished when we have a reaction or a flash of temperature. We see it generated when we have a flash of lightning and things along those lines.

So in this machine, when the nitric oxide is produced, it is attached to the plasma energy wave. This increases the half life of the molecule to about 30 to 45 seconds. Plenty of time for us to be able to get it where we want it to go, to try to treat something that we can see.

The other interesting thing is that when the molecule is attached to the plasma energy, that we have found and others have found, that it will actually penetrate intact skin up to 3 cm. That's about an inch and a quarter or so through intact skin that you can treat disease. We found that we can treat certain infections without having to open the skin. We found that we can treat a number of things under the skin without having to open them up, and sometimes even debrided or drain things like that. It works exceedingly well in killing the bacteria and biofilms because it goes right through and kills the bacteria.

We've also found a number of other diseases that it works very well for, and we are looking at ways to provide that to see that in the future.

So that's how nitric oxide works. It comes through, it unites the nitric oxide, then meets with the tissues there and through chemical changes and all. It results in death of bacteria, and it will dilate blood vessels and it also is an anti-inflammatory. Which really is beneficial to the tissue, especially if we're trying to get the wound to close.

So watch out for more information about nitric oxide gas that's coming down the pike. I think that as more and more information is found out about the nitric oxide therapy, that you'll find that it is going to be a very, very interesting therapy, and could be very well a game changer. If you want to look at radiation wounds, especially as we've mentioned in the part one of this segment, we have a problem with too much inflammation, too little circulation, and cells that don't work very well. The nitric oxide will stimulate the microvasculature to dilate it and increase the circulation. It works very well to do that.

It is also the anti-inflammatory that we know that will close down the inflammatory response that we see resulting from radiation therapy. And we found that there is some effect on fibroblasts and other cells in the area that's been damaged by the radiation, to treat them so that they will respond a bit better toward healing.

As we talk more about the use of this in radiation wounds, you'll see that we have found that this is probably one of the better treatments at this point for radiation wounds, and we will discuss that in the next segment.