Intermittent Claudication

Chief paper discussed: T Parkington, T Maden-Wilkinson, D Broom, S Nawaz... (2023). Low-Intensity Resistance Exercise with Blood Flow Restriction for Patients with Claudication: A Randomised Controlled Feasibility Trial. Vascular Medicine . Position statement on managing PAD: Askew, C. D., Parmenter, B., Leicht, A. S., Walker, P. J., & Golledge, J. (2014). Exercise & Sports Science Australia (ESSA) position statement on exercise prescription for patients with peripheral arterial disease and intermittent claudication. Journal of Science and Medicine in Sport / Sports Medicine Australia, 17(6), 623–629. Additional papers referenced: Bentzen, A., Nisgaard, L. B., Mikkelsen, R. B. L., Høgh, A., Mechlenburg, I., & Jørgensen, S. L. (2023). Blood flow restricted walking in patients suffering from intermittent claudication: a case series feasibility and safety study. Annals of Medicine and Surgery (2012), 85(5), 1430–1435. Saes, G. F., Zerati, A. E., Wolosker, N., Ragazzo, L., Rosoky, R. M. A., Ritti-Dias, R. M., Cucato, G. G., Chehuen, M., Farah, B. Q., & Puech-Leão, P. (2013). Remote ischemic preconditioning in patients with intermittent claudication. Clinics , 68(4), 495–499. Ahmed, K. M., Hernon, S., Mohamed, S., Tubassum, M., Newell, M., & Walsh, S. R. (2018). Remote ischemic preconditioning in the management of intermittent claudication: a pilot randomized controlled trial. Annals of Vascular Surgery. https://doi.org/10.1016/j.avsg.2018.07.046 Podcast w/ Jamie Burr we referenced: https://owensrecoveryscience.com/podcasts/owens-recovery-science-podcast-bfr-ipc-for-performance-rehab-and-health-w-jamie-burr-phd

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SPEAKER_04 0:14

I'm supposed to clap so you know where the sound comes in, Kyle. We jazz. I you'll know. After all that shit we did at the jazz and probably got nothing because of the damn ice machine behind me. Yeah, it's it's pretty it's pretty brutal, actually.

SPEAKER_05 0:32

Yeah, ice machine. Slime in the ice machine at the Utah, not really. That's uh you got you guys don't know that, do you? Um do you know that, Ben? You might, being from Houston kind of region. Slime in the ice machine.

SPEAKER_07 0:49

Uh-uh.

SPEAKER_05 0:49

You don't know that? There's this legendary yeah, so there's this legendary uh newscaster in Houston. He's passed on. Um, his name was Marvin Zindler. And every Friday night he would do uh like health reports on restaurants around the Houston area. And he always had this bit slime when they found slime in the ice machine, they'd have like graphics and he'd be like, slime in the ice machine, and everybody would you know tune in Friday night after the football games, the high school football games to watch Marvin Zindler's health reports on Houston and restaurants.

SPEAKER_04 1:35

That was Kyle's boring ass Friday nights in high school, the slimy guys, exactly.

SPEAKER_05 1:42

Um, we have to watch this. Yeah.

SPEAKER_04 1:47

All right. Exactly. Welcome to another Own Discovery Science podcast. This is Johnny Owens. I'm here with the crew, Ben Weatherford, Kyle Kimbrell, and Zach Gunkel, who goes by HMFIC. I'll let you figure out what that is. I'm El Hepfe, Don Juan, the real HMFIC, Johnny Owens.

SPEAKER_05 2:06

I know I thought it was Arch Manning's fanboy.

SPEAKER_04 2:13

I've been that, man. I'm just really am now. So yeah. If I can get an Arch Jersey next podcast, I will be rocking that bad boy and Arch element, whatever it takes.

SPEAKER_05 2:25

Shout out, shout out all our listeners uh with Texas Lonehorn Football Connections. Please send Johnny a Arch Manning.

SPEAKER_04 2:32

Our buddy over there, Donald Wynn, doing great work. Let's get those guys fixed, Donald. I'm you know, dealing with an abdominal strain with Quinn, but we're good, man. We're golden. National champions for probably in the next 10 or 15 years, I'm thinking.

SPEAKER_05 2:56

Sounds like Johnny's been drinking what Star Quinn drinking.

SPEAKER_03 3:01

This is like how every season starts.

SPEAKER_04 3:05

Right then happened, maybe now my mind's like, we just won recruiting. Did you see that recruiting?

SPEAKER_05 3:14

Uh Texas longhorns of the new Dallas Cowboys.

SPEAKER_04 3:18

We'll see. Buying all my tickets. Got my Kentucky tickets. So uh yeah. Yeah, they almost beat Georgia. I know, I know. Better be careful. I mean, yeah, I know. We have Georgia in like three weeks or something, so we'll see. Georgia in town and F1 Austin. It's gonna be a nightmare. Oh, the same. Oh wow, same weekend, yeah. Brutal. Are you going to F1? No, no, man. That's that's that's a pricey sport. I don't know if you guys know.

SPEAKER_06 3:53

I don't have any idea.

SPEAKER_04 3:54

I dropped some serious dough last time, but um yeah, yeah.

SPEAKER_05 3:59

They have a whole in Vegas where they did the like, I think where I don't know, the main hub where they take off and finish from or whatever. Like they got a huge plot of land that's just dedicated to that. Uh right that was right off the strip.

SPEAKER_02 4:12

That was a whole shit show in Vegas for Formula One. Yeah, dude, yeah, it was a disaster, man. Like the road was all messed up, the drivers were pissed.

SPEAKER_07 4:22

And then the manhole coming up through the Ferrari.

SPEAKER_02 4:25

Yeah, dude, it was nuts. And then, like, the Formula One people wanted to control the viewing so that people in the high-rise hotels couldn't watch. So they had like these black walls going up, dude.

SPEAKER_01 4:38

Yeah. It was a mess in Vegas.

SPEAKER_04 4:41

Yeah, I'm gonna I'm gonna let them figure out Vegas before I go watch that one because then the damn race was at like three in the morning, which I would either be passed out or drunk or both. So um, that's I gotta I gotta they gotta get their act together in Vegas before I drop that watch. All right, man. So uh any housekeeping stuff, a lot of stuff coming up. I'm speaking at the human weapons system virtually on Friday. What I've got the the uh Defense Health Agency talk in a couple months, Society of Worthopedics Military Surgeons in a couple months, we're doing the Kansas APTA in November. Um, all sorts of cool stuff going on here. You guys, Z, you got that one that um Mark Manyago.

SPEAKER_02 5:27

Oh, yeah, yeah, yeah. That one. But then Mark Manyago and I are doing um the Neuro uh Academy conference uh this weekend in Columbus. Oh sweet.

SPEAKER_05 5:40

Oh, in Columbus, Ohio?

SPEAKER_02 5:43

Yeah, nice.

SPEAKER_05 5:44

I went to Columbus in May. That's a cool little town. Are you where are you staying? Are you staying downtown or yeah?

SPEAKER_02 5:50

I mean it's at the Hilton so conferences.

SPEAKER_04 5:55

Is Mark season any new data?

SPEAKER_02 5:58

Um I think we have some stuff, and then we also have a prospectus paper that has been accepted in the PT Journal. Um that should be pretty good. It's neuro specific, and um I don't know when it's gonna be published. We were hoping it was gonna be published prior to this conference, but um it's been fully accepted. It's just waiting on publication now.

SPEAKER_04 6:19

So Mark's good people, man. Tell him we said what's up.

SPEAKER_02 6:24

Yeah.

SPEAKER_04 6:27

Anything else, fellas, before we get into this paper here? All right, we gotta kind of spin off of other than ortho, Z and Mark doing all the neuro things right now and good stuff. This paper is other than ortho, and it kind of piggybacks off of our Annie Bain talk um that came out what two episodes ago, I think, Kyle? Yeah, yeah, two episodes ago. Dr. Bain with Parkinson's and um that's a badass podcast. She's she's so good and so smart. And one of the things she looked at was um changes with BFR and Parkinson's patients for their vascular systems. And you know, I threw it out at the end, man. I I think the potential of BFR on the vascular system can be huge. Um, that could be something that you know I feel like could be Medicare code worthy if we keep getting papers that show potential, and and it's all pretty straightforward, man. These protocols are like, you know, four to six to eight weeks to see changes in the vascularity. It's either like walking or just doing a simple exercise. Um not super complicated, kind of low-hanging fruit here. And so the paper today that we're gonna go over is actually looking at peripheral vascular disease or intermittent cloudication and blood flow restrictions. So it's from Parkington et al. Um, the title is Low Intensity Resistance Exercise with BFR for patients with cloudication. And it's a randomized controlled feasibility trial. So, you know, what you can get out of that title right there is this is the setup where they're hoping to get a larger multi-center, it sounds like. So this is a feasibility trial. So they want to see is it safe, is it tolerable? But then also, lucky for us on this one, they measured some outcomes which were which were pretty impressive. And so, again, it's in the vascular medicine journal. So went into, I think, kind of a good home journal for them. What they took were people with uh peripheral vascular disease at the I've been working on this all morning, the Sheffield Vascular Clinic in the United Kingdom. Oh boy.

SPEAKER_05 8:25

Oh boy, uh Johnny. Are you missing the uh oh boy, I think you're having internet trouble again?

SPEAKER_04 8:40

Gypsum fries or whatever they want to do.

SPEAKER_07 8:50

Terrible pub food.

SPEAKER_04 8:52

So, anyways, so they use the Sheffield Bascular Clinic um feasibility trial, so it was 30 subjects. 15 did blood flow restriction, 15 in the control group. And again, easy protocols. So it's two times a week for eight weeks, um, and basically two exercises. They did a leg press or leg extensions at uh 20%, right, fellows? 20% of a one RM. I didn't write that down. 20% of a one-ret Max. They followed the kind of the standard protocol 30, 15, 15, 15. And they used a Hawkinson device, uh, 13 centimeters. It's pretty wide cuff. That's what we used originally in the DOD, so these big vascular tourniquet systems, um, at 50% limb occlusion pressure. Um, and so and so that's something that's kind of been consistent in some of these vascular papers is using a lower limb occlusion pressure, which I think when we talk about some of their outcomes, maybe why they didn't see changes in muscle um size or strength. Um, I don't know if maybe this LLP is something with that to discuss. Uh, but basically, yeah, two groups. It was work match, the control group did the same thing, just without blood flow restriction. So, first primary outcome is feasibility. So, can you get people who have poor blood supply who have difficulty walking distance because of their poor blood supply and cloudication? And I guess we should kind of set up the stage here and you guys chime in. Um, peripheral vascular disease is a disease, obviously, of the vascularity, where um, with this cloudication, when you do anything that requires ambulation or effort, um, the lack of blood supply can really start to cause a lot of pain and reduce function. One of the biggest treatments is just graded exercise. There is actually, I've been told, a Medicare code just for monitoring um prefyll vascular disease patients walking on a treadmill and trying to see if they can increase their walking times or doing resistance exercise. But it's very difficult. And I we were trying to get a study going with some vascular surgeons at Walter Reed, and they said these folks just really have a hard time sticking to exercise programs, primarily because they start to have so much pain. They just can't really get through the effort. So the feasibility piece of this trial also is well, BFR is low load. Is this something that would be tolerable and also give these folks some out um some positive outcomes? So on the first outcome of feasibility, they had no adverse events, which is awesome. And you know, we have always heard, especially in the early days, well, this BFR stuff reduces blood flow. So conditions where you don't have blood flow, it's probably gonna be bad for those individuals. We've even heard it said, you know, kind of thrown out, just kind of roll my eyes at it. Healing of structures like an ACL or a tendon, it's gonna limit the healing response. And I, you know, I think we all think it it could be opposite, and we'll get in deep of why we think it really helped these patients, but no adverse events. The adherence to the program was 80%, 81% total. So 78% of the BFR subjects were able to do it, 84% of the controls were able to do the program, no difference between groups, and the completion rate was 90% total. BFR, 93% of them completed it all, and 87% of the controls. Do you guys have any thoughts at first of on that primary outcome of just was it feasible? And you know, I I know we we believe in this, but any any concerns initially on peripheral vaccine doing blood flow restriction?

SPEAKER_06 12:26

Concerns no. I would I can't imagine what we would be concerned about.

SPEAKER_03 12:32

I mean, I think it's for me, it's always been the uh the fear avoidance side of things of we don't really know. And then, you know, for us, it's it's always been the you know, at least internal joke about intermittent cloudication and the walking program, it's like, well, you know, they're kind of already getting the feelings of BFR with walking. You know, do we do we need to add something to that? And you know, who knows? Because we haven't really seen it done.

SPEAKER_04 12:58

So um but since they have such a limited blood flow supply already, just taking the rest of that blood out. Was there any thought that maybe they just wouldn't even be able to complete, you know, do 75 reps for two different exercises, so 150 reps with you know, they're almost maybe at an IPC point, um, even though you know you're led into that.

SPEAKER_05 13:20

I think that um I think we have like a really poor understanding of how these people recruit muscle and use muscle when they engage in activity. Uh I mean, if you go back to our podcast with Jamie Burr, there's a great clip from that where he starts talking about diabetic muscle and how it just goes anaerobic straight away, which is why they fatigue so fast. So the problem that you're gonna have with these folks that have intermittent claudication is it's not like this just happened overnight. So you have months and years of reduced activity, you know, increases in stasis within the vascular system, you know, lack of use of the muscle, which is gonna cause those fiber types to ultimately shift more anaerobic. Um, and so now you have a crew that doesn't even bother even trying to use the aerobic system to produce energy, they just go straight anaerobic. So I think this is where BFR, you know, provides kind of this novel sort of stimuli that sort of forces you to, you know, engage that aerobic system a little bit by by just stressing it in a different fashion. Those are my thoughts.

SPEAKER_04 14:34

Right. That's always the key point. Everyone thinks BFR is just anaerobic, and it's not. You know, you definitely get both fiber types, and there's been biopsy trials and all sorts of studies that have shown that. So it's not just an anaerobic thing.

SPEAKER_02 14:46

We think yeah, I mean, I think you know, something I'd say with child thought is I think maybe one of the challenges is if that muscle fiber is not getting oxygen to begin with, you know, when you exercise, you know, the the potential would be we would if we're gonna tap into an aerobic type of an effect, we have to do something to shift us in that equation because it's a matter of the blood flow not getting there, type of an issue. Um and then I I think the other thing that you see um potentially as maybe a benefit is um the stuff from Danny Christensen and what he talks about. He talks about it more on the performance side of things, but it's this ability that BFR has to buffer um these this metabolic and metabolite buildup, and we buffer hydrogen, and that way we're able to exercise or perform for an extended period of time. Um, I think that potentially could be an avenue there with them.

SPEAKER_04 15:50

What are the I don't know, you know, none of us have probably worked at some of peripheral gowage disease. What are their contrast to exercise? Is it just pain, y'all know?

SPEAKER_02 16:00

I don't know off the top of my head. I know in the uh the Australian guidelines.

SPEAKER_04 16:06

Guidelines, yeah.

SPEAKER_02 16:08

In that Australian guidelines, it's it's exercise, it is is the the treatment, and then your the advice is progressively increase exercise. And I I think with that you you're not running into um kind of like a like a blood pressure type type of a of an issue or something you know kind of uh that would limit your um the ability to perform exercise or partake in exercise. It it's self-limiting. Yeah.

SPEAKER_03 16:40

Yeah, and that's that position position stand paper that you're talking about, Zach, it didn't really give any specific contraindications. It just said to do your due diligence and screening on the front end, you know, do some exercise testing to determine a baseline, make sure you're checking blood pressure and heart rate to assess somebody's baseline and monitor throughout treatment. And then, yeah, like you said, the the guidelines are basically to try and work your way up to the generally recommended guidelines for exercise for most people, you know, doing your you know, two to three days a week of aerobic activity up to 40 minutes, probably starting with less working up, doing at least two days a week of resistance exercise, but you know, targeting more like three days a week and doing you know multi-joint exercises, especially targeting lower extremities. So, I mean it's it's pretty much they're like we want everyone to be working toward general guidelines for exercise here.

SPEAKER_04 17:39

And just do as much as you can until you can't, and pain stops you, or you just can't go anymore, basically. So, again, just really no fear of putting a tourniquet on these people.

SPEAKER_05 17:50

Which is basically what you do with exercise no matter who you are. I mean there's nothing wrong with exercise. That's what you freaking do.

SPEAKER_03 17:59

Yeah. The only uh the only real novel piece in that position stand paper is the the guidance on intensity based on the claudication pain scale for their walking. It's like you know, zero to five scale, walk at a four, and that's your guidance. And if you can't walk at a four, walk at a two or three. And you know, it's basically like do what you can, and you know, maybe you're starting at accumulating 10 to 20 minutes of walking in a session, then you're trying to get up to 40. So it's you know, it's either that or you can do an RPE-based, you know, resistance exercise at times. Uh, but again, yeah, it's it it there's nothing really that different about what they're recommending, it's just using a different graded way to get there. Okay.

SPEAKER_05 18:47

Well, so that's how we look at it from a from a BFR perspective. I mean, that's kind of how we are looking at what we're doing, you know. Just we're you know, the addition of aerobic exercises and the intention is to stress the vascular system and the cardiovascular system. And that that's all we're trying to do with BFR is provide a stressor to that system. We're just providing it and really in a more localized um and probably, you know, in some respective, specific way. Um so you know, we have we have options with BFR or just ischemic preconditioning to to grade exposure or stress um in a manner that not previously even possible. Um so that you know, from that perspective, I think it's it's pretty cool to kind of think about how BFR might might influence these folks uh in terms of their outcomes. Or BFR slash IPC, if you will.

SPEAKER_04 19:51

Well, 100%. In this first feasibility study, they had no issues with them being able to do it, it looks like. So real high compliance, we're able to get through it. And then let's look at their objective measures that they took. So six-minute walk test, time decladication, pain, their change in their quality of life through self-assessment, and then changes in vasocyteralis size and MDC. Six-minute walk tests. I think this is pretty impressive. 86% of the patients in the BFR group improved their six-minute walk test distance by greater than 35.5 meters, which represents a large clinically important difference. Although I saw some other papers that maybe that was on the lower end at follow-up, and only 33% of the patients in the control group were able to see an increase. So almost 90% of the BFR group increased by 35.5 compared to only 33% in the control. That seems pretty sweet for twice a week for eight weeks. The time to allocation um was prolonged in the BFR group by 44.7 seconds after the intervention, but not in the control group, but only increased by 2.6 seconds. So significant in the BFR group, not the control, and that seems like a big difference between the two, almost a minute compared to just about three seconds. Pain ratings in the six-minute walk test were reduced in the BFR group by 1.1. Um, and it was significant compared to the control group, which is only negative 0.3. Their quality of life was significantly improved in the BFR group. So scores reduced in four out of the five dimensions. A reduction is good in the outcome measure they used. Um, so four of the five were reduced, and overall there was an increase in their self related overall health. They did not see that in the control group, but only one dimension that had score reduction. And then the thing that did not change was vascularly size and MVC. Um, and we can talk about maybe why that might have not occurred. So they didn't see change in muscle. Size or muscle strength, but he did see improvement on all these other functional measures. So thoughts developed.

SPEAKER_05 22:07

Small, small clarification. These are they did not report significance in those. Yeah. Because remember, those of the primary outcome is that feasibility. Which which I really liked about this paper, honestly. Like they they really made a point on multiple occasions to kind of say, look, these aren't significant, but we're going to kind of report these percentages, if you will, to give you an idea that you know of what things kind of laid out.

SPEAKER_04 22:32

But um the you know, that spells up for every good problem. Yeah, my bad.

SPEAKER_05 22:36

Totally missed about yeah, no, it's easy when we're you know, we're kind of used to all these things being done significantly, um, or reporting significance.

SPEAKER_04 22:46

So well, we did a feasibility trial, one of our first papers in the DOD, and we did the same thing and didn't report significance and just reported trends. And umber two said the problem with this study is it's not a study.

SPEAKER_05 23:04

That's the problem with literature. Like, I mean, so many researchers don't even know what uh good research is. Um it's it's wild to me, you know. And well, I mean, I think we've all probably been hit up to review papers at this point. And I'm going, I don't know that I'm really like I can't review the statistics like that. Ain't my skill, you know. Like that hopefully your editor's doing that. Um but yeah, yeah, that's that's that's pretty funny.

SPEAKER_04 23:34

And I guess, you know, we didn't mention it in our course, we talk about one of the first people, persons who looked at using tourniquets for things was Augustus Beer. Um, German surgeon, late 1800s, started putting tourniquets on, inflating them, deflating them to see if they could help with some conditions. And one of the one of the groups that was looked at in America using the beer technique was in the early 1900s up in New York with periphovascular disease. And they would just put the tourniquets on and off all throughout the day, and these people were able to walk longer without claudication symptoms. They had a remarkable improvement in their healing. They're six minutes. This is my 1920s voice. Oh god, Christians did better than the Jews because they did ask you religion, they asked your religious reference in that. Oh, seriously. Oh no. But we always said that'll be my last um accent I'll use today, calls. They we always said, or I said, and that's a badass study in a in a population that I thought could really benefit from blood flow restriction would be peripheral vascular disease patients. And so to increase six-minute walk time as much as they did, their ability to walk without prodigation symptoms, reduction in pain, improve their quality of life, um, all seems like this is moving in the right direction. Again, um, controls didn't really get an intervention. Um, you know, maybe you could do high resistance loads with these individuals and would see a different because this was work matched. Um, but overall, it seems like a good trend. What about not seeing a change in strength or hypertrophy? What are your thoughts on that? Not enough sessions, not enough load, too low LOP. Not enough categorization to the muscle fiber, Chris Fry stuff. That's where I was going.

SPEAKER_03 25:40

That was one of the thoughts that I had, but honestly, I'm I'm still kind of surprised because of how untrained this population likely is. I would I would have thought you would have seen a little bit really in both groups, whether you're doing BFR or not, just because it's eight weeks.

SPEAKER_05 25:55

Yeah, I mean, it's not that long. That's your other issue.

SPEAKER_03 25:58

Yeah, it's not that long. It's not that high of a frequency, but you're dealing with people that are untrained, so the the potential for change is higher.

SPEAKER_05 26:07

But yeah, accumulation of all of that stuff, you know, like you said. I mean, I go back, Johnny. Um, you kind of cut out a little bit when you were start sort of like nod to Chris Fry in our podcast and all that, what you're what you're saying.

SPEAKER_04 26:21

About Chris Fry's point of not having enough capillarization. Yeah, that you know, if the study he did where people that had lower capillarization had the less ability to make changes in muscle strength and muscle size over 12 weeks compared to people that had more normal um or higher levels of capillarization in older folks. And so the muscle is fed by the capillary beds, and the more capillary beds that you have in those muscle fiber areas, the better they would do. These people probably are really limited in that in that area. Exactly. And so and it could be kind of what Chris talked about over this six to eight weeks, the angiogenic effect kind of brings them to baseline enough that they would another, you know, four to six weeks start to see some changes just because they did get some increased capillarization.

SPEAKER_05 27:12

That's kind of what I was curious about. Is like you just kind of wonder like, all right, if they had done another eight weeks, you know, what do you see in that in that time? And you do have accumulation of stuff, like you said, you got the the LOP thing, but but they also capped the maximum LOP at 220 millimeters of mercury. So they didn't, you know, if your LOP was higher than that, they just said, well, 220 was your max, which of course we know um is not gonna work for um potentially a decent amount of people in this trial.

SPEAKER_04 27:45

For me, Mike Massive tree trunk muscle legs on that core 100%. I would have been screwed. Well, what about mechanisms? You know, if you listen to our podcast, you probably heard us uh talk about this, but why would BFR be so beneficial for peripheral vascular disease? All the way from the hypoxic state to turbulent flow to vasodilation.

SPEAKER_02 28:15

Yeah, I mean, I I think um you you look at that, and one of the big things, like you guys were just talking about, maybe why they didn't really get the change and whatever, was the lack of perfusion that they had. Um, and then from there, just mechanistically with BFR, one of the big mechanisms that drives the changes through VEGF or this vascular endothelial growth factor. Um, and uh what we see from that is a significant upregulation over five folds, like two hours just post-exercise, uh, of doing one exercise leg extensions, um, compared to no change out of um a regular low intensity exercise. And even at that acute marker, um, there's no real effect, even with high load exercise at two hours. And then um they reassess that, you know, out to um say four hours in that and Veg F's upregulated six and a half fold. Um, so you get a huge increase in this angiogenic growth factor. And then you take a look and you kind of say, well, what does that acute change ultimately lead to is if if we continue this out over a training period? And that's when Jacob Nielsen, you pull his data where he had individuals perform 23 training sessions over 19 days, and um he collected biopsies at baseline, the midpoint of training, which was training day eight, and then continued on to um three days post-exercise, another biopsy, and then 10 days post-exercise. And you could surmise that that acute rise in that growth factor led to um a 24% increase in capillarity by the eighth training day. So we get a surge in this in capillary beds, an increase in perfusion. And that ultimately can help going back to what we talked about. One of the big issues that you have with people with peripheral vascular disease and their inability to exercise is driven by the their inability to perfuse the tissue that's that's working. And so this might be an avenue there. Um, and then, you know, we talked, you know, kind of hinted early on as well about either um this ischemic preconditioning type of an effect or um like the ability to buffer hydrogen a little bit better so you can perform for a longer duration. And that's where some of the work has actually been done within this population is going through and testing, doing incremental treadmill tests. And um, it certainly looks like IPC or remote ischemic preconditioning may have an avenue of acutely boosting someone's ability to exercise. Now, what that looks like over a training period, I think is yet to be seen, but acutely there certainly is an effect there. Um just real quick mechanistically, where that might come in and what IPC does is it basically conditions cells to be more resilient during a period of prolonged ischemia. And so they can function and better utilize the energy means that are generated from aerobic means with oxygen. They can do that for a little bit better in a prolonged period of time before they transition into that anaerobic environment. Um, and then ultimately uh without getting too deep into the weeds, you you get this inability to maintain these um ion channel uh pumps that rely on ATP to function. And once that happens, that's when you know basically the progression into cell death and all that stuff occurs. But I think mechanistically that that's where things uh I think largely are we can have an effect with BFR.

SPEAKER_04 31:56

Yeah. Did you guys see the I think what it was? I wrote it down this morning, 2018 study analysovascular surgery where they did an RIPC, and this was an intermittent codicans exercise or RIPC and exercise. And RIPC, they all improved and there was no difference between the groups. So basically, instead of exercising, if they just RIPC'd, their outcomes were the same as the exercising group after about a month. Interesting. That's an interesting approach too. So they just came in, I think it was every three to four days and did ischemic preconditioning, or they did their strengthening exercises. But the combo didn't improve anything any better.

SPEAKER_03 32:42

Well, and the other mechanism that we didn't really talk about that I typically think of also is the shear stress component or that change in pressure within the vasculature. And and you know, with these things in in the population we're talking about, I wonder if some of the effect of these mechanisms is blunted because of the disease state, right? Like, okay, we think about veg F and HIFLINA and these things being regulated by hypoxia. Well, these people are already already in kind of a hypoxic state. So I wonder if you know, same thing from a shear stress component. I wonder if we're not getting as much change because there's not as much compliance in the vascular system. And so maybe, maybe like, maybe there just needs to be, like Kyle was bringing up, maybe it's a longer time frame that we need to really see some of these things. And then also in that position, you know, paper on exercise for claudication, they brought up, you know, you see improvements in exercise capacity and performance without necessarily seeing changes in the vascular system or the ABI, you know, and so maybe those are not you know always directly correlated with one another.

SPEAKER_05 33:58

You know, they probably do have some hand-in-hand function there, but um Yeah, there's always that piece of do people just get better at tolerating discomfort?

SPEAKER_03 34:07

Right.

SPEAKER_05 34:07

You know, that's always like the argument with stretching studies is like, oh, people just got they didn't actually change the length of the muscle, but they just got better at tolerating that sensation, and so they are able to you know stretch a bit farther, right?

SPEAKER_03 34:21

Yeah. So I mean, I'm I'd be curious to see. I mean, and obviously Annie's stuff goes along with this, and she actually did see some signs of vascular improvement. So it it just seems like now the next step is getting studies that actually measure you know more of what's changing on the vascular side and what's changing on the functional side.

SPEAKER_04 34:43

So that's what I think is badass with all this vascular stuff. It seems like the change happens quicker than I ever would have thought. You know, it's been like four to four to eight to twelve weeks. You know, I was thinking like vascular, like, gee, it's gonna take like a year for all that stuff to change. And I mean, it's it's like weeks. It's crazy. Faster than muscle.

SPEAKER_02 35:05

Well, you know, hold that thought a second. Um back to what Ben was saying was one of the things I wonder too is if if it's like joint OA, and when a joint is so far gone, it's gone. And you can do stem cells, you can do all these great things, but the joint is gone and you're not gonna save the joint. Um, and I just wonder, too, like, you know, if you take a look and and and if you can stratify people based off of whether it's ABI or you know, their ability, their incremental treadmill testing, and then say like, and start grading people on a scale and saying, like, oh, these are the people that are you know, the initial onset of the disease. We can have a really good effect with them with this treatment versus when people are at the end, we just may not get the change that you know we think we potentially might.

SPEAKER_05 36:04

Um yeah, that I I see where you're coming from, Zach. There, I think the only kind of caveat to that is um like we know the vascular system has regenerative capability to kind of regenerate itself back to normal versus like I remember when Johnny, you know, first kind of came out our way and was was teaching uh what taught us BFR, um, you know, it's kind of one of the points he would make with regard to muscle scarring down. It's like it scars down, but it doesn't actually necessarily fully regenerate, you know. And you you have those TGF beta pathways that kind of jump in, where like if the same thing happened in your stomach or the lining of your intestine and you got a little nick and these scar pathways jumped into action, that'd be deadly and problematic. But we have these stem cells that can kind of come in and repair and regenerate. So you gotta you gotta, I mean, it's certainly a possibility, but I also think all right, but we do know that the vascular system can at least kind of repair and regenerate itself better than than other structures, like like a joint surface, for example.

SPEAKER_04 37:12

It makes evolutionary sense for sure. Yeah, um that bascular, yeah. You know, like even John Craig used to talk about the the collateralization that can happen can be rapid as well. Um so it's there's an IPC study showing that. Yeah, maybe they just start to build up these collaterals when they hit a dead end.

SPEAKER_02 37:32

The um the other thing that I was gonna say on these muscle changes and vascular changes, I really think they go hand in hand, and and I would maybe even speculate that that vascular change is what drives the muscle change. Um, you kind of hinted on it with um Chris Prize stuff. Um, but man, there's a ton of muscle stem cell research, or not tons, but there's more than one paper out there that has looked at muscle stem cells and capillary beds. And the muscle stem cells that are closest to the capillary beds, whether we're talking old people or we're talking young people, those are the ones that activate and proliferate. And then you take a look at um Jacob Nielsen stuff, the increase in capillarity, training day eight was the first time it was tested, 24% increase in capillarity, and then you have a 293% increase in um PEC 7 or muscle stem cells in type 1, type 2 fibers. Um so the that, and and then you know, then you can take a look. Other papers have looked at the relationship between muscle stem cells and muscle hypertrophy. Roughly 49-50% of the variants in muscle hypertrophy is driven by muscle stem cell content. So um I think like that that's the deal.

SPEAKER_04 38:54

Yeah. I don't know if y'all remember me talking about Josh Winkey at the ISR. He was a big, it's all about the capillary beds. That's where the stem cells live. That's it. But again, it's just like mechanistically, that's like one of the biggest no-duhs with BFR. And that we can move that needle so rapidly, it's like, man, we this is something. If you if you have vascular clinics out there, will someone start treating patients with this and let me know how it goes so we don't have to wait and die a multi-center trial? Because I would love to just have a vascular clinic with a freaking leg press and a treadmill and some BFR, some Delphi systems in there, and and just do these little interventions. I I just feel like there's potential. Well, on that point, would y'all go at it differently from uh aerobic, have them do like a walk program or bike versus uh resistance? You know, we've seen that in different styles of the studies because there's that Benson. I don't know if y'all saw that case series where they did walking and they they had similar results and ABI increased as well. Ankle breakers.

SPEAKER_03 39:59

They just did one leg, but they did 12 weeks instead of eight weeks. So it was longer.

SPEAKER_05 40:06

Which I mean, I think I I think we would expect you would have to do that, you know, to kind of um get similar results.

SPEAKER_04 40:14

They do four times a week, they do four times a week because it was a European study and they all take off on Fridays and don't do shit. Um we could learn from that even in the summer when nobody's working at all. Every time I email people from there, they're always out. Um Luke Hughes um Stephen Patterson. Yeah, hashtag Luke hashtag Stephen.

SPEAKER_03 40:42

Uh um I don't know. I for from a vascular standpoint, my my brain kind of does go a little bit more toward the aerobic or endurance-based activities just because we see more of those doing a bilateral, and we see more of those doing a longer duration under hypoxia, which in my mind would be a bigger stimulus on the vascular system. Whether or not we actually see more vascular change, I don't think we really know that uh conclusively. But I mean, from a logical standpoint, it makes some sense.

SPEAKER_06 41:21

So I think you just have to figure out what the person can do.

SPEAKER_03 41:26

Yeah.

SPEAKER_05 41:27

You know, I mean, in the end, Johnny, back to your kind of original question there, you know, what do you what would you do? That that would be that would be my thought is well, let me just find out what I what what can this person do, but maybe more importantly, what can I get them to do? You know, um, and that's where that's so that's why it's like I I keep kind of mentioning this IPC thing because I envision, like, you know, as a clinician, somebody comes in your clinic and you're like, oh, maybe let's try this BFR thing, but you can't figure out where to start because the person's so you know limited. Um, and it's like, well, maybe you can just teach them to get comfortable to the cuff being on them, you know. I mean, once the cuff's on them, you can always have them clench their muscle a little bit. You could have them move their. There's there's loads of different things that you know you could kind of try um and still be able to grade with regard to the occlusion pressure or the activity that you're given that individual until you get them to the point where it's like walking on a treadmill or exercise or something like that.

SPEAKER_04 42:40

Maybe I haven't seen it, but it feels like this would be an interesting study. So you IPC, and we know that you get an increase in braiding kinine and adenosine. Um, so you get this vasodilation effect just from IPC. And so we see some of the IPC, you do a pre-performance, you see performance improvements from that vasodilation. Just with an IPC patient, could you? I mean, a peripheral vascular disease patient, IPC them, then have them go walk and increase their ability just to walk from that. I mean, that's an easy protocol. And there's already a Medicare code for walking with these people.

SPEAKER_02 43:15

So that's what um this paper by Say's did.

unknown 43:19

Yeah.

SPEAKER_02 43:20

They that they they tested that Johnny is fine.

SPEAKER_04 43:23

Shit on that was my idea for a real illness study.

SPEAKER_02 43:26

Well, sorry, I mean maybe you could replicate it. But no, that that's so crazy enough, like that that's um what what they ended up doing was they separated individuals into three different groups and just did incremental treadmill testing um under th three different conditions. So they they walked on a treadmill first and then they they brought them back like a week or so later, I believe. And then um then they had them do I uh remote IPC uh and then walk again. And look at the distance at which they walked. The second group did RIPC first during the first session, walked, and then came back a week later and then just walked again. And then the third and final group straight up just walked on the treadmill regularly each session. Just to look at basically, is there some sort of training effect going on? So basically, are people just getting better on the second session, regardless of what's done?

SPEAKER_04 44:26

So this was with peripheral vascular disease?

SPEAKER_02 44:29

Peripheral vascular disease, yeah. Um, and so the treadmill uh test was walking at um 3.2 kilometers uh per hour, whatever that translates to in uh miles per hour. But um, and then they the treadmill was increased two percent every two minutes until that person said um they they tapped out and said, I'm done. Um outcome measure that they looked at was the um initial cloudication dish distance. So like when they started to feel their symptoms, and then the total distance that um that they were able to walk. Uh RIPC was your standard standard five minutes of ischemia, five minutes free perfusion cycle, three total times. This was done in the upper extremity, and um it was done 90 minutes before the treadmill testing from here. So this is just an acute deal. And um and then what they found was there was a significant increase in the first group that um did the RIPC treadmill second. There was a significant increase in that distance walked. Um, the um the second group that did their RIPC uh treadmill test first, they walked for a significantly greater distance um that session than what they did the second session. Now, there was um a little bit of a training effect in that everybody or the group C did increase the um the distance that they walked over the second session, but um it wasn't um or the group A that did I R IPC second walked a significantly greater distance than what group C did in that um in their second session. So what we're getting at or what what this ultimately goes to show was uh RIPC it appears to have an effect. Um we see that when RIPC is performed with that treadmill walking, they're able to walk um for a greater distance um prior to the onset of symptoms.

SPEAKER_05 46:39

So if we were to build a hierarchy of how to approach patients from the absolute most limited scenario up to resistance exercise loaded at say a 30% one rep max, how would y'all how would y'all split that up? Do you think? How would you approach it?

SPEAKER_02 47:02

So real quick, maybe and I'll tie that in with what Ben was saying before and with maybe this avenue with uh RIPC or IPC, I think one of the key factors is the sheer stress on on the vessel wall, and and it's the inflation and deflation, I think is is is a big player here. If you remember um the um the paper from Danny Christensen when he was looking at GLUT4 transporters and all that stuff, he had a straight-up hypoxia group that was just breathing um like hypoxia air. I believe it was like 9% or something, maybe 12% oxygen. Either way, what happens is is it was the the group that was cycling with the tourniquets on that has the greater um GLUT4 migration to the um to the cell wall. And so what I'm getting at is hypoxia itself does not explain that change. It was the the um sheer stress on that vessel wall that and believed to be the inflation deflations.

SPEAKER_05 48:08

So maybe the the avenue so a function of the vasodilation that you're gonna get, which one of those IPC studies showed actually, like they IPC'd one arm, but you got vasodilation in the contralateral limb that wasn't even right, so you know, which is interesting to kind of think about, yeah.

SPEAKER_02 48:29

That was my next slide we saw driven by like endothelial nitric oxide and and and such. And so I think maybe the hierarchy and how we would manage a patient in with this situation, see what they can do, like like you guys said, but then if they're really limited, we just go through alternate inflation deflation. If they don't tolerate the aerobic exercise or right away or at all, and then I think doing a few um exercises, resistance exercises with the cuff on. And that way, you know, if you do the IPC, you're getting um three rounds of inflation deflation, and then if you can target three to four exercises, that's another three, four inflation deflations. Um, and you should be inflation deflation, Zach.

SPEAKER_05 49:18

But be let's be specific here arm, leg, percentage of occlusion pressure, etc. Yeah, I think LOP is interesting for this.

SPEAKER_02 49:26

Yeah, I mean, I I think I I would try to target um in the leg the the higher pressure, um, and that goes back to the Mauser paper. Um, and what they found was 80% limb occlusion pressure produced the changes that the lower limb occlusion pressure did not change. Um, so I I would try to try is the key word when you manage the patient, but I would try to have a higher pressure in the cuff. Uh now that wasn't tolerable or whatnot, and then we can kind of reduce it down from there.

SPEAKER_04 50:01

Yeah, I think so. Like stick to our same guidelines. If they don't tolerate it, go lower, because a lot of these papers are using like 50-60 LOP, but it's just I think they're nervous to go higher. And you wouldn't when you set up a study, you don't want to screw yourself and have a high dropout. It doesn't mean 80% wouldn't do better. It's just you got to make sure they tolerate it.

SPEAKER_03 50:24

And going back to your question, Kyle, of hierarchy and how would you you know implement it? Seems like starting with the passive inflation, deflation, like we've talked about, is the place to start and know that it's gonna be easier to tolerate it. And I mean, uh going back to what we discussed in the history of BFR and we kind of alluded to early on of just passive inflation, deflation, improving walking tolerance and pain and wound healing and all that, it's they were doing a pretty low pressure for a very short amount of time. They were using 80 millimeters of mercury for two minutes on, two minutes off. And but they did it for a long duration. It was like 12 hours a day. So maybe that's the the give here is you could either maybe push for a little higher pressure, have less you know, inflations and deflations, get it done in a shorter amount of time, or if you need to go lower pressure, you probably need to take this and spread it out over a longer time in a treatment session, you know. And so that seems to be the the give, at least from the limited information we have. And maybe, you know, especially in this population, maybe starting with uh BFR on the upper extremity because it's not where they typically have their exercise symptoms, maybe that would be a way to introduce it and have them tolerate it, experience it, and then we transition to the lower extremities. And we could do some something like you know, recumbent cycling or walking, start start with a lower pressure to introduce it, make them comfortable, do it in an intermittent fashion. So again, it kind of makes it something that's more tolerable. You know, maybe we start with something like 50% occlusion, like the Parkington study did, yeah, and then work our way up.

SPEAKER_04 52:16

So Ben, you were talking about that 1920s paper that I mentioned earlier.

SPEAKER_07 52:21

Yeah.

SPEAKER_04 52:22

Because they also found that five out of the seven patients made it to the cafeteria and could get a sarsaparella. One patient remarkably was able to do that.

SPEAKER_05 52:32

Oh, your internet, your internet's cutting out.

SPEAKER_04 52:41

Oh, in the Napoleonic Wars.

SPEAKER_05 52:48

Uh somebody else has joined the chat, apparently.

SPEAKER_04 52:51

Lots of potential here. Lots of potential. Yeah. Not with that. No, I'm saying with the study, not with my 1920s accent. So man, I hope these guys get a multi-center. It sounds like what they're what they're going for over there. I don't know. Do you guys know these folks at all? I'm gonna have to reach out, see if we can know the no, okay.

SPEAKER_06 53:14

No.

SPEAKER_04 53:14

Well, I think the potential is huge for this, really easy to do. And if if we're improving people's vascular systems, that that that's a big game changer. And then hopefully we can throw some strength and hypertrophy on there. My granddad had peripheral gasper disease. It's miserable, man, because he was a real active dude. And you know, he would just work for a few minutes and have to stop and put his legs up, rub his legs, rub castor oil on whatever the heck he would do, um, to try and get better. But it's it's a miserable, miserable way to live, especially if you're trying to do a lot of things. Cool. Anything else you guys want to add? I know Castle's got a bunch of people.

SPEAKER_05 53:54

We do we have we do have some questions. Um, I was just gonna say that the one thing I that I don't think we really discussed um with regard to uh not seeing increases in strength or hypertrophy is they they estimated a one-rep max, but I I didn't have and they and they reassessed it every two weeks. Um but I don't even have uh the image that they said described how they estimated it. So we don't really know if they truly were like really close to like a 20% of one rep max or not, you know, depending on depending on how they estimated it.

SPEAKER_03 54:34

Um it it's seen they meant made some mention to RPE, but I don't know if that's how they estimated the rep max.

SPEAKER_02 54:47

They they did it based off failure. Yeah, but with how many reps? Well the yeah, the the problem though is um they cited another paper they did. I think they said Yeah, the the the problem that you run into with stuff like that is when you're doing a yeah, when when you're basing your rep max on a high number, it's just gonna really impact. That's my point. The other thing with that too, Kyle, was I think they did um the traditional set of 30, 315s on a leg press, but only three only three sets of 15 on the leg extensions. I think it was the permanent.

SPEAKER_06 55:36

I wrote that they did all 75 reps, but I I definitely could have missed that. Sometimes these things hide.

SPEAKER_02 55:43

Yeah, no, patients perform four sets of 30, 315s for the leg press, followed by three sets of 15 uh repetitions for the knee extensions at 201RM. So yeah, you know, maybe maybe a volume thing there. Well, that you know, and then when you're trying to assess, yeah, you're only doing 45 reps, and the exercise that you're you know looking for there's another study that did something very similar to that.

SPEAKER_05 56:11

Um I think it was like the that Abe paper or something way back in the day.

SPEAKER_06 56:17

Um but anyway.

SPEAKER_04 56:19

Yeah, but that was their test was leg extension strength as well as basis lateralis. So if you're only doing those three sets, it might not be enough volume. Like how many of those subjects actually even completed that volume? You know, from ours, it's like and we did 30, 15, 15, 15. Yeah, it's like, yeah, not for the first couple weeks.

SPEAKER_02 56:42

So Kyle, they did um they used the Brazaki formula is what they based off of.

SPEAKER_05 56:48

But again, but you gotta you still don't know how many reps they did, right? Well, how are you gonna report that?

SPEAKER_02 56:55

It was to failure. So I mean the problem is you don't know what the load was. You know what I mean?

SPEAKER_05 57:03

Well, my point is like you're gonna, I mean, if if you're failing at around 10 rep 10 reps, that's a around about a 7% one rep max, but that's the predictive value of those things, is like if you can do more than 10 reps, they lose accuracy. So if they were doing like a 15 rep max or a 20 rep max, plugging in the formula, that is not gonna be as accurate as if they had done like a five rep.

SPEAKER_04 57:26

Half the papers don't tell us how they get their one RMs, really.

SPEAKER_02 57:29

Yeah, yeah. So they increase this. Is the other paper they did increase until momentary muscle failure occurred within 10 reps.

SPEAKER_07 57:38

Okay.

SPEAKER_04 57:39

And so you just don't know like um, but they use it appropriately, you know, as uh they did the Brizicki um formula, like did all the division themselves or just use an F.

SPEAKER_01 57:52

You know what?

SPEAKER_02 57:54

That fucking form uh that I'm sorry, that freaking formula.

SPEAKER_01 57:58

Um go ahead and edit that out.

SPEAKER_07 58:01

No, no, that's it in there, bitch.

SPEAKER_01 58:06

Dude, that that formula has too way too much math in it.

SPEAKER_02 58:10

All you gotta do is the load times the max number of reps multiplied by 0.033333 repeating and add the load back in. Dude, it flows in the calculator on your phone, simple.

SPEAKER_04 58:24

And that's why like why people use that Bersicki formula, it's I don't know. Ridiculous. Like that's I mean that's not calculated to me. Yeah, all it has is some division, and who you know, once you start putting parentheses around the numbers, I'm screwed.

SPEAKER_01 58:38

Yeah, I mean it's like, dude, who has an Excel spreadsheet pulled up that you're just gonna plug, dude? Just make it simple.

unknown 58:44

Yeah.

SPEAKER_04 58:45

Or use the one already calculated. Use the app.

SPEAKER_06 58:48

Yeah, use the app.

SPEAKER_04 58:51

All right, man. Again, good stuff. Hope we get more of this. And if anyone is doing this with patients out there, please let us know. I'd be very interested to see real life kind of how this is going. Yeah.

SPEAKER_00 59:05

Thanks for listening to the Owens Recovery Science Podcast. Owens Recovery Science is a single source for PCs, OTs, ATCs, DCs, MDs, and other medical professionals seeking certification in personalized blood flow restrictions rehabilitation training. Find them online at OwensRecoveryscience.com.

SPEAKER_05 59:28

One last thing before we get out of here. First, I want to say uh sincere thank you for listening all the way through. But also wanted to remind you that this podcast should not be considered medical advice. It is strictly entertainment. It's a way for us to try to keep up with what is ongoing within the BFR world. If you require some sort of medical attention, medical advice, please seek that from a licensed individual within your state. Thanks and we'll talk to you soon.