Gladden longevity — Episode #57

Steve Reiter: Welcome to the Gladden Longevity Podcast with Dr. Jeffrey Gladden, MD, FACC, Founder and CEO of Gladden Longevity. On this show, we want to answer three questions for you: How good can we be? How do we make 100 the new 30? And how do we live well beyond 120? We want to help you optimize your longevity, health, and human performance with impactful and actionable information. Now, here's today's episode of the Gladden Longevity Podcast.

Dr. Jeffrey Gladden: Welcome, everybody, to this edition of the Gladden Longevity Podcast. I'm seated here with Dr. Paul Harch. Dr. Harch is a, probably, I don't know if you're considered the godfather or the grandfather or the father of hyperbaric therapy, but certainly, you have tentacles that go back in time, and you've been working with hyperbaric oxygen for a long time. There's a lot of buzz around hyperbaric oxygen, not only for its healing properties but also for its rejuvenation properties or purported rejuvenation properties. And it'll be interesting to have this conversation with you. So, welcome to the podcast, Paul.

Dr. Paul Harch: Thank you. Pleasure to be on.

Dr. Jeffrey Gladden: Yeah. Great. So, just to start to give the audience some sense of context here, maybe you can give us a little bit of your background. How did you get interested in hyperbaric oxygen and when was that, and what drew you into this?

Dr. Paul Harch: That's a great question. I was in a general surgery residency and had a very severe accident, an auto-pedestrian accident. I ended up taking a medical leave and, during that time, had accepted a job temporarily-

Dr. Jeffrey Gladden: Let me get this straight. You got hit by a car, is that what you're trying to say?

Dr. Paul Harch: Yes.

Dr. Jeffrey Gladden: Okay. So, you got hit by a car, and you got beat up pretty good. So, what got hurt? Your head?

Dr. Paul Harch: A lot of things.

Dr. Jeffrey Gladden: Including your head?

Dr. Paul Harch: A lot of orthopedic stuff, back, yes. Ended up with burns and some amputated toes, fractures.

Dr. Jeffrey Gladden: Okay.

Dr. Paul Harch: Yeah, I don't know. It probably should have killed me, but I managed to survive. Anyways, long story short, I ended up taking a temporary medical leave to have another operation, and in the process, I'd accepted a temporary job in New Orleans in emergency medicine. And I ended up in an emergency medicine group that was South Central United States and Gulf of Mexico referral for all diving accidents and had the option to learn diving medicine since, as you well know, none of us are taught that in medical school. And I went and got some training in it. And so, started this foray into diving, and an integral part of it was hyperbaric oxygen therapy. And what intrigued me-

Dr. Jeffrey Gladden: Let's just explain that to the audience. Why would hyperbarics be used in diving medicine and scuba divers? Maybe you can just walk them through that for a second.

Dr. Paul Harch: Well, anytime you go underwater, which is under increased pressure, our tissues take up and store the inner gas we're breathing. So, the nitrogen in our air is taken up in our-

Dr. Jeffrey Gladden: Yeah. About 80% of the air we're breathing is nitrogen, right?

Dr. Paul Harch: Right. And we take it up and store it. And when you then come up from your dive, scuba dive, or whatever, you have to release that, and you have to come up slowly. And even when you do come up slowly, about 5% of that gas is thought to separate out as bubbles into the bloodstream, into tissues, et cetera. And it turns out when you have too much of that and exceed your clinical threshold for symptoms, people get what's called decompression sickness, and the treatment-

Dr. Jeffrey Gladden: Yeah. The bends.

Dr. Paul Harch: Correct. The bends. And what people don't realize is that 80% of the bends is not the bends, the joints; it's spinal cord and brain involvement. And so, the treatment for it is to go back under pressure. And that's been the treatment since 1900. But in the 1930s, '40s, and '50s, US Navy decided and started introducing oxygen into the decompression, thinking that that might speed the resolution of the bubbles, and in fact, it did. And out of that, and some other roots used in the Netherlands for hypoxic conditions, carbon monoxide poisoning grew the subspecialty of hyperbaric oxygen therapy.

Dr. Jeffrey Gladden: So, why would this work for carbon monoxide poisoning? Explain that to your audience, how, I guess high pressure oxygen is going to push that carbon monoxide off the hemoglobin and put oxygen back in, is what we're thinking.

Dr. Paul Harch: That is one part of it, yes. So, the carbon monoxide binds to our hemoglobin, and displaces oxygen 250 times more avidly than oxygen does. So, you end up hypoxic, and when you give oxygen at pressure, the amount of it is able to displace that hemoglobin. But, in addition, it has a wide range of effects on the pathology that's caused by the carbon monoxide poisoning.

Dr. Jeffrey Gladden: Sure. It's actually probably directly pushing oxygen into the tissues, even irregardless of the hemoglobin. So, you're getting some oxidation that way.

Dr. Paul Harch: It is. And if you deliver it quickly enough, meaning within the first hour after pulling somebody out of the carbon monoxide environment, a large part of the injury from carbon monoxide is what's called reperfusion injury, which you well know, but our audience is... The inflammatory reaction of the body to reestablishment of circulation after a deprivation of oxygen or blood flow, and that, in fact, is more damaging. And if you can give a hyperbaric treatment almost immediately in that hour period, you can almost knock out 90% or more of the reperfusion injury.

Dr. Jeffrey Gladden: Yeah. This was the same thing in cardiology, of course, with heart attacks; if we could get the artery open fast enough, we could minimize the reperfusion injury. And there are strategies, and that's interesting for the audience to understand when a tissue doesn't have the oxygen that it needs, doesn't have the blood flow, which is bringing the oxygen, it starts to die. And if you reestablish blood flow or bring oxygen to that tissue, because the tissue's already been partially damaged, it has a hard time handling the oxygen that's coming in. And so, the oxygen being an oxidant actually can accelerate the damage that you're bringing oxygen back to try to alleviate. So, you get caught in this catch-22 of doing the right thing but still causing more damage in the process of doing it. And so, there have been many strategies around how to mitigate that reperfusion injury. One of the things that we have been thinking about is molecular hydrogen as a way to modulate reperfusion injury.

Dr. Paul Harch: Yes. Right.

Dr. Jeffrey Gladden: And I'd like to do a trial of that at the heart hospital, but I've got too many other things going on at the moment.

Dr. Paul Harch: Sure. But that's part of actually the paradox, or it's another hyperbaric oxygen paradox that you were talking about a little bit earlier. The idea of giving tons of oxygen with hyperbaric exposure in this immediate inflammatory period has always offended the medical profession, thinking you're doing more damage than good, meaning throwing gasoline on the fire. But, in fact, it quenches the reperfusion injury. And there's now extensive literature on this.

So, getting back to how I got into this, it was with looking at these divers and asking questions about what was going on in their brains and which the US Navy had pretty much ignored as part of the decompression sickness component. But, in fact, the bubbles go through the brain within minutes, and the reperfusion injury is what's dominating the reaction or the problem. And what we found, and what I discovered back in the literature buried, was that this acute treatment in the first hour that was curative for 90% of people with at least brain and body decompression sickness. In fact, we were treating reperfusion injury in the brain. We weren't treating bubbles. And that-

Dr. Jeffrey Gladden: Yeah, that's interesting. That's really interesting because now, when you think about reperfusion injury, basically, one of the things is the reactive oxygen species are triggering damage, but it's also triggering inflammation to occur, which actually generates more reactive oxygen species at the tissue level and perpetuates the damage. So, is the hyperbaric oxygen coming in and taming the inflammatory cytokines that are released, or is it actually doing something relative to the tissue in another way?

Dr. Paul Harch: Bingo. In fact, that acute hyperbaric treatment, what's been found is the primary target is polymorphonuclear neutrophils. So, the acute inflammatory cells that now come into the tissue damage express receptors on their surface, beta2-integrins, which attach to the inside lining of our smallest blood vessels. You know this, but I'm just saying it in terms of our audience.

Dr. Jeffrey Gladden: Sure, sure.

Dr. Paul Harch: And what happens is those white blood cells now stick to these inside lining of the tiny blood vessels, and they essentially clot them off. And so, what happens, and what's been shown, is if you can give that hyperbaric treatment in the first hour, it totally inhibits those attachment molecules on the white blood cells from expressing themselves. And the cells just roll right through. So you maintain circulation. And so, what it's doing is treating the white blood cell-mediated portion of the acute inflammatory reaction. And that-

Dr. Jeffrey Gladden: It's almost like you just turned off the fire alarm, right?

Dr. Paul Harch: Right-o.

Dr. Jeffrey Gladden: The white cells are rushing in to put out the fire and clean up the mess and all that, and then you basically dump in the oxygen. It's like, ‘oh, there's plenty of oxygen here. We can stop getting so excited.’ It's like stopping the firemen from breaking into the house.

Dr. Paul Harch: Yes, it quenches the reaction. It's almost like the CO2 fire extinguisher, but we're using oxygen and not CO2.

Dr. Jeffrey Gladden: Right. Okay. I get it. And so, that was interesting for you because now, all of a sudden, you're starting to see that. Obviously, their joints are important and critical, but their brain supersedes that, of course. And so, did you start to see better clinical outcomes in these people, or what was the story there?

Dr. Paul Harch: Not until the second component of this took place, and that was, I kept asking questions: ‘What's going on in their brains? Are there bubbles?’ Nobody knows the answer. ‘Well, okay, we just treated the guy, he's not all better. The US Navy says 90% of them are cured now. This guy's still got symptoms. Are the bubbles gone?’ Nobody knows. ‘Well, how many treatments do we have to give him?’ No one knows. You just keep treating.

The reality was all of the coastal facilities that treat divers do not get the same results the US Navy does. Often you have to give additional treatments, and nobody could answer this. And to me, I mean, I was just completely baffled, why are we not getting the same results? And the answer was we weren't treating the same thing. We're in New Orleans, we're 90 miles upstream from the Gulf of Mexico. By the time divers get in from the Gulf of Mexico, it's by sea, by land, maybe they can sleep it off, show up the next day, three days later, and now we're treating different pathology, we're treating the results of that reperfusion injury, tissue damage, ischemia, et cetera.

And what I found out was that if I dropped the traditional high dose of oxygen to a lower level, that the Germans in the '70s had shown acute severe traumatic brain injury and acute stroke was more sensitive to, these divers got better, and we had better neurological outcomes. And then it became: “What else could work? What other chronic or subacute injury?’ And we started looking at boxers, simultaneously, with this discovery.

Dr. Jeffrey Gladden: Let me interrupt you for just a second because this is interesting on the oxygen. Because when somebody comes in for hyperbaric therapy, acutely, in the room air that we're breathing, it's 21%, 20%, depending on your altitude, it can drop down to whatever is, I think it's 6%. But, of course, with hyperbarics and high oxygen, how much oxygen would be in there? Above 21%? Was it 50% or higher, or where were you going?

Dr. Paul Harch: Oh, no, it was 100%.

Dr. Jeffrey Gladden: 100%. Okay.

Dr. Paul Harch: So, the standard was 100% O2 by mask or entire chamber content at pressure. So, let's say you're at two and a half atmospheres, it's 250% O2.

Dr. Jeffrey Gladden: Okay. Exactly. Just so the audience understands, oxygen is... Everything is kind of in its own balance. So, water is good, but too much water is bad. Oxygen's good, not enough oxygen is bad. Too much oxygen is very toxic.

Dr. Paul Harch: Exactly.

Dr. Jeffrey Gladden: Just like too much water is very toxic. And so, when you're adding all this oxygen on top of the other injury, maybe you're turning off the fire alarm, but that much oxygen can actually perpetuate its own damage, so to speak. And so, that's-

Dr. Paul Harch: Correct.

Dr. Jeffrey Gladden: ... kind of what you're talking about here. So, then Paul was basically, Dr. Harch was turning down that concentration of oxygen to something lower, not to 21. Where did you turn it down to?

Dr. Paul Harch: Well, no, we turned actually the pressure down.

Dr. Jeffrey Gladden: Turning the pressure down.

Dr. Paul Harch: It was still using pure oxygen, and this is in the day before I had come across the information that probably the equal or greater benefit in this therapy was due to the pressure itself, not the oxygen.

Dr. Jeffrey Gladden: Got it.

Dr. Paul Harch: And so, what happened was we dropped the oxygen pressure down from standard 2.4, 2.5 atmospheres to roughly an atmosphere and a half, which is the equivalent of breathing pure oxygen going 16 and a half feet underwater on a scuba dive but with pure O2. And now it's a whole new world because of the realization that pressure is, in fact, a bigger component. And you may not even need the huge amount of oxygen depending on your condition.

Dr. Jeffrey Gladden: Right. Because if really what you're trying to do, well, you're trying to do two things. You're trying to push the nitrogen back into the tissue, so that requires pressure. And then you're trying to use oxygen to sort of quench the reperfusion elements and the inflammatory elements. So you're trying to balance two variables here to control two different sides of a problem, is what I'm hearing.

Dr. Paul Harch: Well, partly, but the other thing is the concept of barometric pressure, which has not been appreciated for the 362 years of this therapy. Barometric pressure is a totally separate entity from the oxygen, and it took the FDA for the first time looking at hyperbaric oxygen under the drug section in 2008 to suggest this. Nobody in my entire career in clinical hyperbaric medicine had ever suggested anything that pressure was bioactive. But it turns out it's in a category like a temperature. It's a thermodynamic intensity parameter and a completely separate entity. And so, it turns out it is the dose of pressure and the dose of oxygen, and the two are independent, overlapping, and interactive. And that's now been shown with gene expression. It's like a whole new world with hyperbaric oxygen.

Dr. Jeffrey Gladden: Yeah. That's beautiful. So then, have we gotten to the point where depending on the presentation of the person, the timing, the insult, et cetera, that you can dial in the right pressure and the right concentration of oxygen to treat that particular disorder?

Dr. Paul Harch: God, what a great question. That is where we are, where I am trying to take this field right now, is that the whole idea of dose and trying to personalize this has been completely beyond anybody's mentality for the history of this because no one understood how it worked. So, what happened is, and you'll appreciate this, it is the only specialty in medicine outside of experimental protocols where it is protocol-driven. ‘Oh, well, what worked for diabetic foot wounds?’ ‘Well, I treated it this way.’ ‘Okay, we'll try that.’ Pretty soon, you have a cluster of people that got better given a certain dose. So, diabetic foot wounds, what do you do? ‘Oh, that's the protocol.’ ‘Well, wait a minute. I'm an individual. I'm different from others, my diabetes may be-… my foot's different, my vasculature, my wound is different. I'm going to get the same exact dose, though.’ And now the appreciation is, ‘wait a minute’, and especially with the brain, this is going to be a matter of trying to find what your brain is responsive to. And that's what I'm doing with quantitative EEG right now.

Dr. Jeffrey Gladden: It should be possible to do this, I would think, in an experimental animal model where you dial up different things and start to measure gene expression, cytokine, all these different things and look at recovery times. And then from there, you start to postulate rather-

Dr. Paul Harch: Yes.

Dr. Jeffrey Gladden: ... that for this injury, we're going to do this with this percentage of oxygen and this level of pressure. I mean, it almost seems like if you had enough data, you could get an AI program to kind of spit that out for you.

Dr. Paul Harch: Eventually. Yes. And this is kind of what's been done, but sporadically over decades, even hundreds of years. So, 300 years of hyperbaric air therapy that predated all of this oxygen, hyperbaric oxygen, and that the idea of dosing, it's been sporadic in places, but no one has really finally put it together or even used it as a primary method of treatment.

Dr. Jeffrey Gladden: It seems to me one of the challenges there is actually being able to look at the gene expression. I mean, that's relatively esoteric testing, and we're doing it now in the aging process. We're looking at transcriptomics and proteomics of aging to see what are we actually accomplishing. Are we making somebody's DNA express itself in a younger fashion or not? But I can tell you, in the longevity space, it's taken me a while to get to that point where we could get this developed to the point where we could bring it forward. And I think it's got to be true in your field, too, that this is what you want to get done, but it's got to be difficult to do, right?

Dr. Paul Harch: Unquestionably. In fact, if you look at the 362-year history of this, the first concept of hyperbaric oxygen as a DNA signaling drug came about in '94. And it was out of a rat model, or excuse me, a rabbit wound-healing model a group of doctors in Minnesota and St. Louis were investigating, and over the subsequent, oh, 14 years, there were individual articles that targeted a single gene hyperbaric treatment to see if it upregulated or downregulated. Well, in 2008, Dr. Cassandra Godman, up in Massachusetts took chemo endothelial cells, single treatment mass gene array analysis, 8,101 of our 19,000 protein-coating genes. And now there's been a series of experiments on that.

Dr. Jeffrey Gladden: So, almost half, 45%, roughly, of the whole protein-coating genome, let's say, its regulation altered. Probably some up, some down, but it's altered, right?

Dr. Paul Harch: Yes, exactly.

Dr. Jeffrey Gladden: And so, it's fascinating to see just how when the body is stressed, what the magnitude of the response is. It's really such an intricate system.

Dr. Paul Harch: Unbelievable.

Dr. Jeffrey Gladden: It's really an intricate ecosystem. And when we go in, and we say: ‘Well, we're going to manipulate this gene, or we're going to use CRISPR, and we're going to pop this one out and pop that one in…’ I smile for several reasons. One: I'm so passionate about the intent of that. And then I smile for another reason, like: ‘Oh my gosh, we're so underestimating the ecosystem that we're working in.’ Right?

Dr. Paul Harch: We so do. This is actually a favorite topic of mine. It goes to our discussion about HIF-1-alpha earlier. You look at these 19,000 genes, a coating for all of these proteins-

Dr. Jeffrey Gladden: Let's define that for the audience. We were talking prior to the start here about the hypoxia-inducing factor, and it came up in a conversation because there was a paper written out of Israel that I read, and there are other papers that Dr. Harch knows about where they were talking about the paradoxical impact of oxygen in that it's hyperoxic, sort of external to the tissue, but at the tissue level, it was actually releasing hypoxia-inducing factor, which would be indicative of the fact that at the tissue level, it might be hypoxic or low oxygen, so high oxygen outside the cell and low oxygen inside the cell. And maybe that stress was related to the lengthening of telomeres that they saw, maybe, I don't know. There are lots of questions about that paper, and to me, it never really covered a lot of water.

Dr. Paul Harch: No, I agree.

Dr. Jeffrey Gladden: But we have much better ways to lengthen telomeres, quite honestly, than that, than sitting in a chamber five days a week for three hours. But anyway, back to this, you brought it up, the HIF. So, what were you going to talk about this hypoxia-inducing factor?

Dr. Paul Harch: Well, I was just trying to make the point of what you're making about the genome. If we put all of the human biochemistry on the wall and all these reactions, you could wallpaper a couple of rooms with it. And our approach in allopathic medicine is we're going to throw a dart at that one reaction there and think we're going to get a blocking agent or some drug, and it's going to ameliorate this lifestyle, chronic illness. To me, it's humorous. It gives a lot of people jobs and all of that, but it's not realistic.

Dr. Jeffrey Gladden: No, I agree. Yeah, I agree. It's completely unrealistic. So, I think one of the things that we have seen in the longevity space is kind of the utility and health giving benefits of what we call hormetic stresses, which are stresses that actually push the system. They don't break the system, but they allow the system to actually respond to that and get stronger. Do you feel like hyperbaric is also... I mean, I know the baric element of it, the pressure element of it is probably hormetic stress. We see genes activated to that. Do you think the whole thing is kind of a hormetic stress as well in terms of the regeneration that occurs?

Dr. Paul Harch: Unquestionably. In fact, you're familiar with- You're talking about essentially about hypoxic or ischemic preconditioning.

Dr. Jeffrey Gladden: Right.

Dr. Paul Harch: There is a whole literature now on hyperbaric oxygen therapy preconditioning where giving this up to 24 hours ahead of time, in fact, protects the organism against a subsequent ischemic and/or even traumatic insult, et cetera.

Dr. Jeffrey Gladden: Okay, let's just stop there for a second because the audience just got lost. What we're talking about here, let's say that you're in a lab and you have an animal and you have their heart, and you take one of their heart arteries, and you tie it off with a string, and all of a sudden there's no blood going to a section of their heart, that heart tissue starts to die very quickly. But if you precondition the animal, if you close the artery off for 30 seconds and open it, close it again for 30 seconds or a minute and open it, do that three or four times, and then seal it off completely, you've preconditioned the artery, now the heart attack is much, much smaller. The body has adapted to that and opens up collaterals and things like that. And you can precondition arteries by releasing nitric oxide, giving nitroglycerin, using things that will produce nitric oxide. And we're talking about hyperbarics here now as being a pre-conditioning stress that would mitigate what would happen if an artery were to be closed off, right?

Dr. Paul Harch: Exactly. And so, going to what we talked about earlier with the effect on white blood cells, which is a dominant part of any reperfusion injury, any tissue injury, and so on. What has been done with, for instance, carbon monoxide poisoning, is that if you give a hyperbaric treatment within 23 hours of a carbon monoxide exposure-

Dr. Jeffrey Gladden: Exposure.

Dr. Paul Harch: ... within the previous 23 hours in a rack, you can almost inhibit all the damage done by the carbon monoxide.

Dr. Jeffrey Gladden: Oh, wow.

Dr. Paul Harch: Yes.

Dr. Jeffrey Gladden: That's amazing. I've not heard that.

Dr. Paul Harch: Exactly. So now, hold on, I'm going to give you one more little one, a little tidbit here. We wanted to do this with coronary artery bypass surgery.

Dr. Jeffrey Gladden: Sure.

Dr. Paul Harch: Your area here. We used to call it ‘pump syndrome’ and such after bypass, and you go in the ICU and here are these people, they're no longer having their rest anginal pain, and yet they've got these long, drawn faces, they look like they've had decompression sickness, and we now all know it's the effect of bubbles and other stuff and many things going on during bypass.

Dr. Jeffrey Gladden: Sure.

Dr. Paul Harch: What's been shown is that if you give two hyperbaric treatments the night before cardiac surgery, you have a significant reduction in that cognitive insult that occurs with bypass.

Dr. Jeffrey Gladden: Beautiful.

Dr. Paul Harch: Published out of England, 1995.

Dr. Jeffrey Gladden: Beautiful.

Dr. Paul Harch: We had a study we wanted to... Yeah. Couldn't get it funded, though, in the late '80s or '90s.

Dr. Jeffrey Gladden: That's spectacular. And what were they using to do that? Is that 100% O2, or what was it?

Dr. Paul Harch: Yes. Yes. And I think it was 2.4 atmospheres or somewhere around there. It was 2005. I'm sorry, I think I said '95, but yeah, 2005.

Dr. Jeffrey Gladden: Cool. Well, that's fascinating. So, now you started a practice that utilizes hyperbarics, and you're located... Tell people where you're located.

Dr. Paul Harch: We're in New Orleans. And we're at this little remote clinic that grew up kind of because of the whole diving industry. And actually the end of this next month, in February, I'm moving across the river to another part of New Orleans, but we're in the New Orleans area.

Dr. Jeffrey Gladden: And so, out of that experience in the emergency room, when you got introduced to this whole field, then you basically made this your life's work is what I'm hearing. Is that correct?

Dr. Paul Harch: I did. And what happened was I saw my mentor, who really is the one who introduced me to this, Richard Neubauer, in South Florida. Brilliant man published a lot, but he never got any significant traction. In fact, he got a lot of criticism for a variety of reasons. But the main one also was he was doing it in a freestanding facility, no institutional support or attachment. And so, we realized that we needed some institutional coverage for credibility. So, we started a fellowship at LSU. And so, we've had an academic appointment there, and all of this work I've done has been done at this clinic, but the formal studies have been under LSU's IRB and so on. So, it's kind of been a two-track job, and the third was the teaching component of it.

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So, let me ask you this. At any of the LSU hospitals, are they doing hyperbaric prior to cardiac bypass surgery?

Dr. Paul Harch: No.

Dr. Jeffrey Gladden: No. Okay.

Dr. Paul Harch: No.

Dr. Jeffrey Gladden: Have you given a grand rounds on this?

Dr. Paul Harch: Oh my god, yes. I've talked about this. We've shown this years ago. The main problem-

Dr. Jeffrey Gladden: Isn't it fascinating?

Dr. Paul Harch: It is, but what's the nuts and bolts of it? It boils down to reimbursement. It is not reimbursed, so there is no way they're going to do it.

Dr. Jeffrey Gladden: If you don't think your doctor is handcuffed and your hospitals are handcuffed to the insurance payers, there it is right there.

Dr. Paul Harch: Oh my god.

Dr. Jeffrey Gladden: They are handcuffed. They are led by the nose by the insurance companies. It's a tragedy, quite honestly.

Dr. Paul Harch: Well, look at our training programs. What are we trained in and taught? We are taught reimbursable medicine.

Dr. Jeffrey Gladden: That's right. That's exactly right. Yeah, it's super sad. But anyway, so what are some of the innovative things you're doing in your clinic to help people? Give us some examples of that.

Dr. Paul Harch: Well, probably the most innovative is the way I'm trying to dose initial dosing to brain activity live. For the first, roughly 13, 14 years, we formally investigated and tied this therapy to brain blood flow imaging. And we used a provocative test that had been published once, brain blood flow scan next day in the chamber at a given dose of hyperbaric therapy. And then patient comes out, and we rescan. We did this for a good amount of time. Five and a half years, it was under a formal study, and it was very good. If you saw an improvement in brain blood flow on that second scan, I had 100% predictability guarantee, and it didn't matter what the neuropathology was or their disease, I could improve that patient, and I would tell them that. I'd promise it to them.

But the problem was that second scan was always three to four hours after they came out of the chamber. It was the delayed effect of what happened in the chamber. What I've now done is adapt quantitative EEG, so standard 19 lead EEG. And I do that before they go in the chamber, and then I put them in the chamber, and I take them through a dosing profile of five different doses of hyperbaric therapy, look at the brain live, record it, quantitate it, and then study it to find where I am best-impacting brain function. And that's where we start treatment.

Dr. Jeffrey Gladden: Okay. Well, I love the precision of that. I guess I have two questions about it. One is: it sounds like they're wearing an EEG cap while they're in the hyperbaric the whole time while you're adjusting the levels of pressure and oxygen.

Dr. Paul Harch: They are.

Dr. Jeffrey Gladden: So, you're getting real-time feedback.

Dr. Paul Harch: Yes.

Dr. Jeffrey Gladden: And then the second question, well, there are three questions. The second question is: What are you looking for? Are you looking for an increase in electrical signal? Or what are you actually looking for?

Dr. Paul Harch: If you look at QEEG, there is massive quantitation that is derived from that. And you look at the absolute power of the different bands of electrical currents. So, we have 40 different frequencies of electrical current in our brain all over the place. So, I'm looking to see absolute power, I'm looking for balance. I'm looking to see a global effect on the brain, which is what we saw with decompression sickness, with traumatic brain injury, what we saw in the SPECT brain imaging, and finally looking for connectivity. So, much of the brain diseases are caused by problems in the white matter, for our public, the connecting tracks that connect all the brain cells. And there is a way of looking at that connectivity with EEG, and you can quantitate it.

Dr. Jeffrey Gladden: Right. So, I like that a lot. So, then I guess the question is: if you do the EEG after they come out of the hyperbaric, let's say you did it two hours later or three hours later or the next day, would the effects be durable on some level? Or is it more of an acute event that stimulates healing, but what you see in the chamber actually dissipates over some period of time? How does that work?

Dr. Paul Harch: That's a great question. There is permanence and transience to that effect of every single treatment. And so, for the hyperbaric virgin who's never been in a chamber before that you're treating for the first time, the majority of it through that first block of treatment is permanent. And as time goes on and you do additional treatments, there's more of it that is transient. We're inducing a change that doesn't have as much permanence to it, but there's so many targets, and there's so much tissue pathology that it's impacting that you can't pinpoint exactly what's going on. I would just give you the gene expression argument part of it. And if we look at the SPECT brain imaging, the sweet spot for seeing that improvement in blood flow and brain function after they came out of the chamber was somewhere in the range of two to 10-12 hours later. But the effect is often there the next morning to some degree. And, yes, symptomatically, it will dissipate, but with the gene expression, what's been shown with a single treatment, you have gene expression going on for up to 48 hours. And that was just a limited experiment.

Dr. Jeffrey Gladden: Right. Interesting. So, I guess one question would be on the dosing or the timing of the dosing, would you wait 48 hours or not? And the other question that I had prior to that is whether- We do EEGs in our practice also, and what we see is that there are parts of the brain that are hypoactive and parts of the brain that are hyperactive. Does the hyperbaric, does it have a balancing effect that you see when you're doing this or [inaudible 00:35:33]?

Dr. Paul Harch: It does. It has a number of effects. If you look at what we saw with brain blood flow imaging, take the veteran study that I published, we saw a huge increase in brain blood flow in the group as a whole after one treatment, with that scan done about three to four hours afterward. But at the end of 40 treatments, all done in one month, so pretty much I compressed it, the overall average brain blood flow was unchanged, but the highs came down, the lows came up, and it had a more normalized-looking appearance to it. And so, the EEG, yes, we're changing things, but like wounding, you wound yourself right now, the timeline for healing that wound is at least a year. Look at plastic surgeons and when they'll want to remodel a wound or revise a scar. Most of the change is in the first six months, 85% of it, but it's in constant evolution. And so, depending on where you intervene, you're hitting a moving target, and the hyperbaric oxygen has its own timeline to it as well.

Dr. Jeffrey Gladden: Have you ever coupled this therapy with other regenerative technologies like exosomes or stem cells or peptides or anything like that?

Dr. Paul Harch: Indirectly, but not at my clinic. And the reason is, I've told people: ‘if you come here, we're going to have one variable and answer one question; is this therapy going to work for you or not?’ But ultimately, yes, synergy and multimodality therapy is the ultimate. And so, I have a lot of my patients who are also getting stem cells while they're here. They get them from another facility. In fact, there's a lecture I can point you to where I summed up all of this. There is now an accumulating literature on hyperbaric oxygen therapy effects on our own stem cells, from proliferation, migration, implantation, and every phase of it, to effects on administered stem cells.

So, from another source, or let's say you take them from yourself, now re-inject them IV, hyperbaric oxygen, if you couple it with it, has been shown to facilitate implantation. So yes, my patients get other therapies, but not generally here. They're coupled with it subsequently. And when I do long-term care, often it's... In fact, in Texas, a great example, I've got a patient who did EEG neurofeedback with continued hyperbaric oxygen, and the case report was just published last year.

Dr. Jeffrey Gladden: Well, that's fascinating because I've done some neurofeedback. And neurofeedback, it's interesting, but it doesn't seem to have quite as much stickiness as you would like. You can feel effects acutely, and you can feel effects kind of a little bit cumulatively, but it just doesn't seem to have the stickiness that I would like.