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Medical Mysteries Explained · Acedra
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Medical Mysteries Explained
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0:00
Good morning. It is 2:56 a.m. Welcome back to the hospital at night. I've just finished my 11th or 12th case of the day. I'm going to try and skull off to bed. I'll leave my registar to fend for himself. He's a big boy. He can manage. But before I go to bed, I wanted to share um two extremely curious phenomena with you in medical science that remain poorly understood to this day, especially the second one. their fields of ongoing research, including my own tiny contribution to the field. The
0:33
first is something that will sound completely counterintuitive, where reality is exactly the opposite of what you would instinctively expect. And the second is a discovery that is equally fascinating and that promises so much, but um well, we'll get to that. I've often thought about sharing this stuff, but I figured it's a bit niche or academic, so I don't know. But well, I thought while I'm in my no frrills video era, it will be a good chance to share some science, which is indeed cool, but
1:02
most importantly doesn't require me to do any research before recording because I already know about it. And there aren't many fields that I know enough about to speak without looking anything up. And since I didn't think you wanted to hear me talk about cricket or 1980s synth music, I'll stick to medicine. And I chose something that I know especially well and is the is it it's the field that I did my PhD research in. So I'll start by setting this in well. This is
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this is kind of like I like Hank Green's sitting at a desk explainers. So this is my tribute act albeit with more pauses for breathing. Your arteries carry blood to your body. Occasionally they block. Well the treatment for that seems obvious. Unblock the artery. And that is indeed what I do. a little insight into the high level of comedy and rep RT that I inflict that I I treat my patients to is I usually quip that I'm ultimately just a plumber. >> You're not a plumber. I'm a plumber.
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>> But what if I told you that the act of unblocking that artery, whether it's supplying the heart, a kidney, a brain, or a leg, actually caused more damage. This is something called reperusion injury, and it really does boggle the mind. Heart attacks continue to enjoy tremendous popularity among the general population and ensure that my job is effectively recessionp proof and I think probably AI proof as well at least until I retire which frankly cannot come soon
2:25
enough. Heart attacks of course are arterial blockages. Evolution in all its foolishness decided that this organ that has to beat continuously your entire life. It cannot even stop for a few seconds or you die. And thus it requires a constant supply of juicy oxygen rich blood at all times. And by the way, the organ that supplies that blood is itself truly the most hustle and grind organ who would doubtless post inspirational ticker tick tocks preaching self-sufficiency if it wasn't so busy
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working around the clock supplying the whole ungrateful body with blood. Even the stupid brain whose sole contribution is cake, cigarettes, and a constant supply of stress that literally no other part of the body is thankful for. or the liver who just shovels toxic cholesterol out like waste oozing out of a sewage processing plant. Don't even get me started on the mouse who hasn't met a chip it didn't like. What about the pointless pancreas who has like two jobs
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and manages to balls up both of them? And then we come to the sorry sausage of sick that calls itself the bowel, the microbiome. Shut the Apparently that's a trigger for me. So evolution or whichever incompetent drunk designed the heart's blood supply decided that this organ that cannot stop should be supplied by weedy little arteries that have a prediliction for blocking. Now when one of these arteries blocks interrupting the blood supply that's a heart attack. Now most heart attacks
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cause some damage to the heart but the artery spontaneously opens up again. :00lock passes and in um you know they're a bit more stable. But in many cases the artery remains blocked until it is unblocked by people like me in places like this. There are these are the major class of heart attacks and these are the ones that cause the most harm. So they're the ones that need emergency treatment. Now you might think that the damage is done when the artery oludes that the blood supply is cut off
4:19
and the cells which consume large amounts of oxygen and nutrients. Heart cells are metab metabolically very active. They have high numbers of mitochondria quickly become eskeemic which means starved of oxygen and then they become necrotic eventually which means they die and that's true that does happen that is a source of damage but there is a two hit phenomenon. Now you might have seen some news recently that the death rate the mortality from heart attacks has plummeted over recent
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decades and it's an incredible success story. It's it's what few areas of medicine have seen such an amazing transformation. Indeed, one that really inspired me to go into the field. Those of you under the age of about 30 might not realize that before the year 2000, heart attacks claimed so many young lives. People in their 30s, 40s, 50s, you know, just dropped down dead. I mean, I'll put some charts on the screen, but look at the the reduction in deaths. It's it's truly amazing. This is
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thanks to better medication, better inpatient outpatient care, better nursing, better rehabilitation after heart attacks, better pacemakers and devices, and of course, the rolling out of emergency stinting procedures, which have saved millions of lives, and perhaps just as importantly allowed me to start a YouTube channel predominantly based around me being in the hospital at night. But we are now very good at opening up arteries. We manage that within about 20 minutes of a patient
5:38
arriving. In many countries, if you have one of these major class of heart attacks, you no longer go to your local hospital. You come somewhere like this to a heart attack center. And but that's only half the equation. The reperusion injury that I mentioned seems to inflict a second hit on the tissue that was up until that point starved of oxygen. The very process of restarting blood, the blood flow has directly caused damage. So why and why does this only occur in
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some cases? These questions fascinated me so much that I ended up going into the field and my projects were looking for ways to prevent this. Now, you might wonder if we know it does harm, why even bother opening up the artery? And that's a a fair question, but we know that overall opening up the artery is definitely the right thing to do. In many cases, patients would simply die if you didn't. Um, and most of the time, like in all my patients today, for example, as soon as you open up the
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artery, the patient stabilizes, they immediately look better. They feel better. And this is one of the reasons I love interventional cardiology because I'm one of the world's most impatient people and immediate results are my love language. Hello from the daytime. I've actually spent the last few days trying to recover some inexplicably corrupted video files. I don't know what went wrong. So I I managed to salvage all of it except for this little chunk. So what
6:57
I was saying during this point in the video was that sometimes a patient's pain actually gets worse when we open up the artery. And you can imagine this fills them with dread. They've come into hospital with a huge heart attack and then some clown whose jokes are middling at best. Um has actually made their pain worse. And it's demoralizing for the treating team as well. The last thing I want to do is inflict more pain or injury on a patient. But that's literally what's happening. And
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something I sometimes use to explain to patients is not physiologically an accurate analogy, but I think it helps kind of sort of frame the problem. You know, when you sometimes sit in an awkward position, you don't notice your leg going to sleep, but when you stand up, that's when you get the pins and needles and the pain. And it's a similar kind of phenomenon. It's when the blood starts flowing again. Um, of course, pins and needles in your leg is not caused by the blood being cut off to
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your leg. It's more to do with the nerve being compressed, but you get the idea. I think it's a useful framework to help people understand. It could be summarized as saying, you know, things get worse before they get better. In fact, that's kind of the TLDDW for this whole video. So, what is actually going on? Well, we don't fully understand, but we know some mechanisms that are involved. As oxygen and nutrients are cut off to their cells, then ATP levels fall. Now, ATP, you'll remember, is the
8:16
kind of uh energy currency used by the body. The tissues become acidic. and the me the um little pumps that you get in the cell membrane, the ion pumps that regulate the concentration of sodium and potassium and things like that fail. You get an intracellular buildup of sodium. This draws water into the cells and that's edema or swelling. So the the tissue becomes very adeous, inflamed and swollen. metabolic activity starts winding down and the cells like fish out
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of water gasping for air start to fade and die. But then when the artery is opened up, boom, reperusion. Suddenly a red tsunami of oxygenated blood cascades in and bathes the vascular beds in what they've missed so badly. And yet this brings a second wave of destruction. Incomplete reduction of oxygen in damaged mitochondria produces reactive oxygen species. That's oxygen with a unpaired electron in their outer orbit aka oxygen free radicals, super oxides, hydrogen peroxide, hydroxil radicals,
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they're all formed. They they all damage tissue. They cause things like cell membrane dysfunction. The lipids or protein and DNA damage, inflammatory pathways are kicked into overdrive. White cells infiltrate the tissue. Compliment which is part of the immune system is the immune response is activated. inflammatory cytoines are released. Calcium floods into the cells. Now, for reasons are too long to go into here, calcium just royally everything up. I mean, to quite an impressive
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degree, cell damage, further reduction in ATP. Calcium, it's like a crazed calcium cowboy that just comes into the saloon and starts shooting the place up. So, not only can the patient feel more pain, but they can also become unstable. or the pumping function of their heart can suddenly deteriorate causing the blood pressure to crash. They can have a cardiac arrest. It does at least ensure that everybody in the room is paying attention. You know, we're quite comfortable dealing with these
10:18
complications and thankfully it almost always passes and the patient stabilizes, but unfortunately the heart does take this double hit. An interesting visual demonstration of this is what we call the dreaded no reflow phenomenon. When you unblock an artery, normally you inject dye and you see the artery suddenly reappear and a big hose pipe fills the screen. Great feeling. But in no reflow, even when you've relieved the blockage and you put a stent in, you inject the dye, nothing
10:45
happens. The vessel simply doesn't fill with dye because the blood in the artery is just sitting there unable to go anywhere because the vascular bed that it's supplying is so swollen and angry and inflamed, the capillaries are all squashed shut. The patients who are most at risk for this are those who waited hours and hours before calling an ambulance as the longer the eskeemic time the less likely you are to get a good result and it is again demoralizing to do all that and then at the end of
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the procedure you get this no reflow. So one of my projects was doing MRI scans on these very severe heart attacks and even the MRI die a few days later still cannot penetrate the area of damage but in the worst cases we actually saw hemorrhage. the blood vessels have ruptured causing bleeding into the heart tissue. And this doesn't just occur in the heart. You can see the same phenomenon in uh the brain after a stroke. Most strokes are caused again by an interruption in the blood flow. So
11:39
technically we to be consistent we should call them brain attacks. But if the blood flow then returns to the area of damage, then you can get reprofusion injury and you can get something called hemorrhagic transformation which is bleeding in the brain. And I'm sure I don't have to tell you that is bad news. And this brings me to attempts to prevent reperusion injury. And the second crazy thing I wanted to tell you about. Back in the 1980s, a decade of course known for its pioneering
12:06
synthesizer evolution and innovative sampling. Sorry, wrong video. Someone discovered that if you create temporary eskeeia, a little suson of hypoxia a few times before a heart attack, the heart attack is actually smaller. This, as with so many discoveries, was found in animal studies. It was in a dog. So if a balloon was blown up in a dog's cardiac artery for a few minutes blocking it, the balloon was brought down, blocked again, unblocked several times, and then
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a heart attack was caused by permanently blocking the artery. And the heart attack was smaller than if it had occurred without all of that preparation. So that was weird. But then somebody else noticed that you don't even need to blow up the balloon in the same artery that you go on to block. Any cardiac artery will do even if the heart attack is in a different territory. And so somebody thought, well, if it's in a different territory, why not a different organ altogether? Let's not fiddle
13:02
around in the heart, which of course is very different difficult. Why don't we block the artery supply in the kidney? Which is much easier, isn't it? I mean, whom among us hath not blocked a renal artery. So they caused these cycles of eskeeia in the kidney and then the heart attack was still smaller. So what is going on here? Kidney is nowhere near the heart. Then somebody realized you don't even need to do anything invasive at all. You can inflate a blood pressure
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cuff on the arm to cut off supply to the to the hand temporarily just for a few minutes like a toric. And do that a few times up down up down and bingo bango the heart attack is still smaller. This is remote eskeemic preconditioning. So what on earth is going on? Why would temporarily causing a bit of harmless eskemia in the arm mean that a heart attack is in the heart is smaller? Well, in a sentence, we don't really know. There are of course many mechanisms implicated and our understanding has
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grown in a large part due to the research team that I was briefly part of who have been pioneers in this field for decades. But in the interest of time, because it is 3:21 in the morning, I have witted on for this is way longer than I thought. I had to stop in the middle to I brought a memory card that was completely full, so I had to empty it. But I drastically always drastically underestimate how long I'm capable of waffling on for. I won't go into the details but hummeral mediators like the
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release of certain protective chemicals into the bloodstream the nervous system may be involved intracellular signaling pathways enzymes molecules all of which serve to to blunt that uh the reprofusion injury meaning the ATP levels are higher and that whole carpet bomb of chaos that I mentioned earlier is reduced and the first time I learned about this it really did seem like magic and then furthermore if all you need is a blood pressure cuff, which every hospital in the world has. No
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medications are needed, no invasive procedures, no skill is needed to inflate a blood pressure cuff. There's essentially zero cost, zero risk. Why has this not been taken up around the world? Because of course, causing a heart attack in a dog in a research laboratory in planned a planned manner is not the real world. No one knows when they're going to have a heart attack. They can't do this 25minut ritual before they have a heart attack. And by the time the heart attack has started, it's
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probably too late. This was the major study that I was part of, a multic-enter blinded, randomized international controlled trial um to see if remote is preconditioning could reduce the size of heart attacks. And spoiler, it didn't. We concluded that not only has heart attack care improved so much that incremental benefits are harder to demonstrate, but also that starting the cycles of eskeemia in the arm after eskeemia in the heart is unlikely to work even if it comes before the
16:00
reperusion. However, not all eskeeia is unexpected like a heart attack. Think about heart surgery where somebody's heart is stopped before going on a bypass machine. Think about a kidney removed from an organ donor. It will be eskeemic until it is reperused in its new home inside a grateful organ transplant recipient. So these have been areas of interest for remote eskeemic preconditioning as well. But like with all medical research and a reason you should ignore 95% of
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what people like Andrew Hume or Brian Johnson say results obtained in small studies in laboratories and animal pilot studies simply don't translate into the real world. Every small study and proof of concept study we did showed a clear benefit. But when we tested it in the big bad wide world, the results were disappointing. Plus, it should also be said that organ transplant and uh cardiac surgery have improved so much that again showing a small incremental benefit is hard. But
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it continues to be an area of research around the world. I do hope it finds a place. It's I think it's unfortunately developing or developed a rep a bit like um precision medicine or stem cell therapy or widespread driverless cars or India being successful in the Olympics. There's a lot of potential but it's always just a few years away. You know, I've just had a thought. I've gone about this whole thing the wrong way, haven't I? I should have marketed this from the
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start as a wellness cure. It makes so much sense. All this time I've been worrying about a lack of real world data and neutral human randomized control trials. But that no longer matters anymore, does it? There's a forum for medical interventions that lack evidence. Podcasts, unlike stuffy medical journals that are only read by industry shields that who insist on highquality evidence, podcasts positively look for small animal studies and poor quality observational research.
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I should rebrand myself as a wellness guru podcast bro and convince people to adopt my new wearable technology. Put it on the outper arm like a CGM. It works so well. I mean, it'll be nicely branded. It'll cost uh $800 750 with my discount code, but it's basically just a BP cuff that inflates and deflates a few times every morning. I need to drop a Ashton Hall morning routine, don't I? I could say I'm biohacking while meditating or hovering above a pool for a few minutes. Oh man, I always wish I
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thought of this at the beginning of the video. I could have started it off. Well, I guess you are watching a business idea hatch in real time. This is where I make my millions. Get your midlife crisis remote resilience cardiorive prepper tech wearable 3000. Now, surely all those wind bags that wang on about sauners and dopamine and UV light and cellular pathways, they should love this, right? All right, let me know if you even made it this far. It is 3:32 in the morning. It's time for me to go.
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It's been a real torrent of information. I hope I haven't induced any information perusion injury to your brains trash organs that they are. Uh, see you next time. Right. One minute left on the card.
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