Ep. 53 – Lasix in Horses Explained Podcast

Welcome back to The Equine Vet Connect Podcast. I’m Dan Carter here at Countryside Equine Hospital. Got Tori Martin with me today.

 

How are you this morning?

 

Doing well. Doing well. Excited to dive in.

 

It’s going to be an interesting podcast.

 

Our listeners have been asking for this one for I think since we started doing the podcast. It’s probably been one of our number one most requested topics.

 

So we’re going to dig into Lasix, an exercise-induced pulmonary hemorrhage, also known as EIPH. So a little bit of background. This occurs in horses at speed.

 

We mostly see it in race horses, barrel horses, but it can also be seen, we just had one the other day that occurred in a pasture. It was hot, horses running really, really hot.

 

This actually happened. So it’s not just if your horse is racing.

 

Well, and that horse was even a little bit older and had never had this happen before. So things that we’re seeing across a wide range of horses in different phases of their life, too.

 

Yeah, I can even make a case. I haven’t seen it in a jumper yet, but depending on conditions, it could maybe even happen there. But, you know, it occurs at speed.

 

So what actually happens is the pressure inside the lungs two things affects pressure inside the lungs. One is actual blood pressure itself. That’s the blood being pumped to the lungs through the circulatory system.

 

The other is the air pressure.

 

So when you take really big, deep breaths, so if you have an increase in blood pressure and then an increase in pulmonary pressure from taking really big, deep breaths, you can actually rupture the little alveolus, the little air sacs inside the lungs where gas exchange occurs.

 

Yeah, the little capillary beds.

 

Yep.

 

So it can be a real issue, very, very common in race horses. So we’re going to kind of dive into that today, and we’re going to talk about sort of the treatment of choice over the years has always been Lasix.

 

Yep.

 

And so we’re going to talk a little bit about what Lasix is, how this works, the good, the bad, the ugly.

 

So Lasix is a pretty cool drug, furosemide, Lasix being the brand name.

 

But it’s going to be quite… I’ve learned a lot so far. So an interesting story, I always say this, I don’t know if we can put this on the podcast or not, but there’s an old saying, I got to pee like a race horse.

 

Yep. So where that comes from is racehorses that get Lasix.

 

So, you know, it’s like 90 to 92 percent of American racing thoroughbreds receive Lasix, and there’s about 400,000 doses a year.

 

Yep. It is a lot. And basically, one of the side effects is you pee a lot when you’re on Lasix.

 

So if you ever use that saying, this is where it came from.

 

Yeah. Essentially, that happens within five minutes of administration, and they can actually lose up to 4 percent of their body weight just by urinating that volume.

 

So let’s do a little bit deeper dive. Let’s get into EIPH. Let’s talk about what all factors are at play because the pulmonary pressure and the blood pressure rise.

 

Yeah.

 

Yeah. So, I mean, when we’re talking about a horse at speed, obviously, there’s going to be a demand for blood flow to our muscles, and there’s going to be a demand for oxygen.

 

So our lungs are going to be working hard, and our cardiac output is going to be a lot higher in terms of pumping that blood to the different systems in the body that are working and needing that kind of energy load that we’re getting from our

 

bloodstream. So we’re going to have not only an increase in that systemic blood pressure, like we talked about as being a component, but then we’re also going to be increasing that pressure in the lungs because of the demand for oxygen to our different tissues and muscles.

 

It’s kind of crazy.

 

If you ever put a heart monitor on a horse and put them in exercise, you know, at rest, a horse’s heart rate is like 30 to 40 beats per minute. When these horses are really exercising, it’s pushing like 2, 250.

 

Like it is incredible how fast their heart beats. And then the other part is when you listen to these horses after a hard workout, you can actually put your hand on their chest, you can feel their heart beating.

 

You can almost see it. Like it is working that hard. And I mean, it is a massive amount of cardiac output.

 

For sure.

 

You couple that with, so you got more blood being pumped out of the heart, plus you’re starting to get some vasoconstriction or making the blood vessels smaller.

 

And this, the increase in blood pressure is significant. I mean, it is a huge increase. And it’s no different than in people.

 

It’s no different than any other animal. Like you really start exercising. That blood pressure is going to go up while you’re exercising.

 

For sure.

 

So, and like I said, when you, then you talk about those little alveolus.

 

We’re talking about one cell layer thick. And that’s going to be where oxygen crosses into the bloodstream, and that’s going to be where CO2 crosses out.

 

Right.

 

So we’re talking about one cell thick. And we’re talking about this blood pressure going through the roof. Bleeding is, like, I’m amazed it doesn’t happen more often.

 

No, that’s fair because we’re talking about these tiny little capillaries too.

 

Like these are not our big vessels. These are our very small little capillaries that have this high intense pressure behind them.

 

And then to your point are, you know, this very thin wall in terms of, because we need that thin wall to have our diffusion of our oxygen so that we can use it.

 

Yep. And so then we start talking about, like you said, that increase in respiratory rate. I mean, the respiratory rate in these horses goes up tremendously.

 

No different than in us. I mean, you start, you watch somebody that just finished a sprint or just finished a run, that respiratory rate’s up.

 

Oh, I’ve been that person too. It’s worse now. Yeah.

 

It was better when I was younger.

 

I mean, you used to go a lot longer distance. Now, I’m like just hustling out of the truck and I’m like, Ooh, deep breath. Fat and out of shape here.

 

So, but yeah, so, and you think about, when that happens, the pressure inside the lungs from air pressure increases. So it’s really a perfect storm.

 

So if you think about that, that one single layer there in the alveolus, you’ve got this huge amount of blood pressure on one side of the capillary. And you get a huge amount of air pressures on the other side.

 

And it’s like, it’s almost like when unstoppable force meets an immovable object, something’s got to give here. And unfortunately, that’s usually the wall of that alveolus.

 

Right.

 

And we get some hemorrhage into the lungs.

 

Yep. And that it can be a varying of grades too. I do believe there is actually a grading scale based on how much distance in the trachea you see that has actual blood presence.

 

But it can be even just a little bit of bleeding can affect their performance significantly.

 

And then you have your higher grade bleeders that obviously, like those are the ones that oftentimes you actually see blood coming from their nostril and things of that nature.

 

But even if you don’t see it coming from the nostril, they can still have low grade bleeding.

 

Right. And that’s an important thing because some of these like to see the blood from the nostril. Some of them have to put a scope in and go look inside the trachea.

 

Others, the only way we find it is if we do either a transtracheal wash or a BAL. And we find a little cell called a hemosiderophage, which is a macrophage that’s helping clean up any red blood cells. And that’d be a real low grade bleeder.

 

But all those can have a huge effect. So obviously, you know, when this happens, one, it’s going to affect performance. Two, it’s going to increase our risk of respiratory infections.

 

So we’re not going to get into what to do if you had a bleeder today. We’re going to, like I said, we’re focusing mainly on the Lasix aspect, because if we can prevent this, it is way better than having to treat it.

 

I feel like we like to say that with most things in medicine. If we can prevent it, let’s start there. Let’s do that.

 

What’s that old saying?

 

An ounce of prevention is worth a pound of cure.

 

Something along those lines.

 

I think it’s an ounce of prevention is worth a pound of cure. So one of the things, and it’s been around forever, and it’s probably one of the more effective ones and mostly used is Lasix.

 

So let’s talk a little bit about Lasix and furosemide, what it does, how it works. Let’s talk about, let’s start with our big overall effect. Let’s talk about the main reason we use this medication.

 

Yeah.

 

So essentially furosemide is a loop diuretic, and diuretic essentially means that we’re increasing our urine output, which is then reducing systemic blood volume. And the way that we do this as a loop diuretic is in that loop of Henle.

 

So, I mean, I can, you want me to go ahead and deep dive into Henle? Or?

 

You know, we can do a little bit. I mean, you know, we’re talking about loop of Henle, it’s part of the kidney.

 

Right. So at the level of the kidney, you have a lot of exchange of different ions, and then you have certain outputs. So in the loop of Henle, essentially we are reabsorbing our sodium, our potassium and our chloride.

 

And this is in that thick ascending loop, which is kind of the second portion in loop of Henle.

 

Well, let’s start here. Like, I think first we need to understand, like, the beauty of the kidney, right? I love the kidney.

 

You’re going to nerd out on the kidney.

 

I’m going to nerd out for a minute.

 

So we’re there.

 

Go for it.

 

But you know, we start out like in the filtering mechanism, which is the glomerulus.

 

Right.

 

And it just filters everything.

 

Right.

 

It filters everything. And so all your, your sodiums, your potassiums, all the bad stuff is all filtered out.

 

Right.

 

And the loop of Henley’s what’s like, well, wait a minute.

 

Bring it back. Let’s keep some of this good stuff.

 

Hold on. I need some sodium. I need some potassium.

 

Right.

 

I need some calcium.

 

And it’s like, let’s bring some of that back.

 

Sure.

 

Like we did, I know we filtered out all that out, but I actually need some of that.

 

Right.

 

And it knows. And if it doesn’t need it, it just dumps it. But if it’s like, hey, we need this, it pulls it back in.

 

Henley’s a pretty smart guy.

 

Yeah.

 

I like to say it’s probably one of the few organs capable of actually thinking.

 

Yeah. No, that’s fair. That’s a good point.

 

So yeah.

 

And so that’s kind of the basics of that. If y’all want and people want to really deep dive into the kidney and any nerds out there, let us know. We’ll deep dive.

 

You know, after last night, I could get excited about the kidney.

 

Kidney’s pretty cool.

 

I didn’t used to get excited about the kidney, but having to prepare for, you know, the details of the mechanism of furosemide, I stayed up a little too late last night.

 

Yeah.

 

Kidneys are cool. Kidneys are cool. So again, let’s go back.

 

Loop diuretic, working in the loop of Henley.

 

Yeah. So we have this, essentially, symporter because everything is going in the same direction. So we call it a symporter that handles our sodium, our potassium and our chloride.

 

It has two chlorides, one sodium, one potassium. And furosemide actually inhibits this symporter.

 

So when we don’t draw that, all of those ions back into the cell and we leave it in that lumen, which is where our urine is created and excreted from, then we’re going to have essentially water follows, especially with sodium.

 

That’s what we say in a lot of body systems is where sodium goes, so will water.

 

So when we’re inhibiting that reabsorption that has been previously excreted and now Hanley’s coming in to reabsorb it, when we inhibit that, we also inhibit keeping that water in the cell.

 

That water then follows the sodium, stays in that lumen and is excreted, increasing our urine output.

 

So like the way I like to think about it is I’ve filtered all this stuff out. I’ve got a pump in there that says, hey, I need some more of this. So it pumps the sodium potassium chloride, does that exchange.

 

Right.

 

And what I like to say is Lasix, it shuts the pump off.

 

It’s like the light switch, it tells ability, it’s like turns the pump off. It’s the switch on the pump.

 

Yep.

 

Don’t work anymore.

 

Yeah. And it actually does that by blocking one of the chloride receptors on that.

 

It’s pretty cool.

 

And it just says, okay, nope, we can’t do our job.

 

Nope.

 

We’re done. We’re not here today. We didn’t show it for work.

 

Yep.

 

Pump’s shut off. We’re done. Call the maintenance guy.

 

Pump’s not working. Turn it off. And like you said, water isn’t going to follow it, which is why urine output increases in these horses.

 

So.

 

And one thing that I found interesting just to note is furosemide is protein bound, so it’s 95 percent bound to albumin.

 

So we actually need our transporter earlier in that kidney to actually get it to where it’s able to do its job here in the loop of Henle.

 

So that’s going to be our organic anion transporter, or they call it Oat 1, is going to be how we actually get our furosemide in. And then about 50 percent of the furosemide that we get in is what’s actually acting.

 

On those pumps, we’re excreting about 85 percent from the kidney, and we are metabolizing about 50 percent in the kidney of what actually gets there.

 

Makes sense. So again, the way that’s going to basically lead to more urine output, more water output, which is going to dehydrate.

 

I hate to use the word dehydrate because we’re not getting to a physiologic, like we’re not getting to an area where dehydration is a concern.

 

Right.

 

But we are decreasing the amount of blood.

 

Yeah. In the Equine Internal Medicine textbook that has a chapter on EIPH, they’re actually showing from different studies that we’re changing the plasma volume by about 13 percent, even though we’re changing our body weight by about 4 percent.

 

So that and that change is allowing us to actually reduce the pressure in those pulmonary arteries, not necessarily the capillaries specifically, but pulmonary arteries by 10 millimeters of mercury, which is significant enough that we’re then seeing these effects in terms of post race scopes in horses that were previously bleeders.

 

The way I like to look at things is, if you got a water hose and you’re putting a lot of water in the water hose, the water hose has a higher pressure.

 

Right.

 

If you decrease the amount of water in the water hose, pressure goes down.

 

Exactly.

 

So if you’ve got a lot of pressure going through a system, you can either A, make the pipe bigger so there’s less pressure, or B, reduce the amount of water in the pipe, and that will also decrease your pressure.

 

Right.

 

And so that’s basically what we’re doing here is we’re decreasing the amount of water in the system, therefore decreasing our pressure.

 

So if we go back to the lungs, when we’re getting to those capillaries, the pressure at that capillary bed in the lungs is lower, reducing our risk. Because we can’t really change air volume.

 

No. And they need that. They need that because we need to get that exchange of oxygen.

 

We need that CO2 out, we need the oxygen in, and there’s not much we can do to change the air pressure.

 

However, if we give Lasix, we can actually decrease that blood pressure at the capillary of beds.

 

And you’re not reducing your red blood cells that are carrying that oxygen, so we allow to still perform well.

 

Correct. Correct. We’re just getting rid of some of the fluid, and it’s temporary.

 

Um, Lasix lasts about?

 

Four to six hours. Although the research really, past four hours is a lot more limited than in those first four hours. In people, they look at it over a longer period of time, and it seems to be out of six hours.

 

Yeah, horses, because we’re usually doing one time dosage of these pre-race.

 

You’re about four hours.

 

And then, to your point about making the water hose bigger, there is actually a component of vasodilation with furosemide as well, because it’s stimulating some prostaglandins, which are then contributing to vasodilation.

 

So they actually do that at the level of the kidney as well.

 

That’s pretty cool. I actually did not know that.

 

Yeah, no, it stimulates the production of prostaglandins.

 

Nice.

 

So we get some vasodilatory effects as well.

 

So we’re making the pipe bigger, and we’re decreasing the amount of volume in the pump, or volume in the system.

 

Right.

 

And we’re reducing that blood pressure. They actually use this in people. That’s one thing they use with high blood pressure in people, is using these loop diuretics.

 

If you know anybody with congestive failure, or any kind of a heart issue, a lot of them are on some type of a diuretic. There’s a whole host of them. But Lasix is the one we use the most.

 

So, typical dose of Lasix in a racehorse?

 

Yeah. So, in the racehorse, they actually are putting caps on the dose. I think now the cap is 250 milligrams.

 

It used to be 500 milligrams.

 

It was 500 and now I believe it’s 250.

 

Right.

 

And that’s coming out of some of the studies, they’re showing 250 milligrams and 500 milligrams. They’re really doing about the same work. Right.

 

The 250 has a few less side effects, which we’re gonna dive into that. There’s a lot of great things about Lasix. This is how it works.

 

And so you’re like, hey, this is great. I’m gonna give Lasix. My horse is not gonna bleed when it runs.

 

Right. This is fantastic. What more could I want?

 

Well, there’s some downsides to this.

 

Especially, and everything with Lasix that’s been studied, everything’s dose dependent.

 

Yes.

 

So on a lower dose, we’re having more mild changes, and then as we get higher in our dose, we’re seeing a lot more of the good to a certain point, and then the bad as we get too high in our doses.

 

So I’m just gonna hit a quick high level overview, and then we’re gonna dive into why this happens.

 

Sure.

 

So there was actually a study done back in, I think it was 2010. It was done down in South Africa, and I wanna say it had, I mean, a significant number of race horses, maybe 2000 race, almost 2000 race horses in it.

 

And they looked at horses that were confirmed bleeders, and they looked at horses that were not bleeders, that did not have EIPH. And what they actually found with horses with EIPH performed better when treated with Lasix than when they weren’t.

 

However, horses on Lasix did not run as well as those that did not receive Lasix. So, and then the other part of that was, if the horse did not need Lasix and was given Lasix, its performance would actually decrease.

 

So, when you really look at it, I would call Lasix one of those necessary evils if you’re a bleeder. But you’re not getting, you’re not getting an increase in performance in that you’re not gonna be better. Does that make sense?

 

Right, yeah, and that was a big concern in terms of the racing industry, especially in thoroughbreds here in the States, is we don’t want to give a performance-enhancing drug.

 

Correct, and like I said, if your horse is a bleeder, it will help it perform better, but your horse will not, the study showed that horses with Lasix did not perform as well as those that did not have Lasix.

 

Right.

 

So again, I have this question all the time.

 

I don’t want him to bleed. Should I just go ahead and start him on Lasix? And the answer is no.

 

No. No, because you’re going to decrease performance.

 

Yeah, I hate to say it, but you gotta at least bleed once. You gotta prove to me that you need it.

 

I say the same thing all the time. Prove to me you need it, because I don’t believe it’s a preventative. And like I said, your horse will not run as well on Lasix as it will off of Lasix.

 

However, if it needs Lasix because it’s bled, it will perform better.

 

Well, and I think that people have this, this fear of their horse bleeding.

 

And rightfully so.

 

And it’s like, it’s like you always like to say, like if you don’t need it, medicine is essentially poison.

 

Yes.

 

And the way I see it, if a horse is going to bleed, we’re going to rest them for a period of time, usually a couple of weeks.

 

But that’s two weeks, let’s call it four weeks out of your normal performance and all of that, because you got to gear them back up after that and take your time with it.

 

Where, if you’re giving this horse Lasix that doesn’t need it, you’re underperforming for multiple, multiple months, potentially, without even realizing you’re doing it. So you’re actually doing a discer…

 

I know it’s scary to, oh, my horse might have to rest and miss these big shows and things, but we don’t know that they’re going to bleed to begin with.

 

And we could actually be underperforming for a much longer period of time by prophylactically treating for something we don’t know is there.

 

Yes, but that was said absolutely perfectly. Absolutely perfectly. So let’s get into why that happens.

 

Let’s get into why that happens. I think to understand that, we need to know a little bit about the function of sodium, potassium, and another one’s calcium.

 

They’ve actually shown, there was one study that showed that the excretion of calcium has markedly increased in these horses.

 

Yeah, I didn’t come across that one, so you’ll have more info on that one.

 

It continues for days. It’s a small little study that was done, and I was hoping somebody would expand on it more. It was only done once, but they were showing a marked decrease in calcium.

 

But sodium, potassium, and calcium are what make muscle contract. Without sodium, potassium, and calcium in the right balance, muscle does not function at its peak level.

 

And so when you look at what Lasix does, we’re getting rid of these electrolytes.

 

Oh yeah.

 

So if you think about it, this is like exercising, not drinking Gatorade. If you’re just drinking straight water, not replacing those electrolytes, you’re not going to perform as well.

 

Yeah, one of the studies that I looked at, the changes in potassium over the first 30 to 45 minutes was like five times the amount of potassium was being excreted in the urine.

 

And then at about the two-hour mark, where we’re to like about twice the amount, as opposed to like four to five times the amount.

 

But yeah, that the potassium is probably the biggest change in terms of the actual numbers when it was being tested is that one is dramatically increased.

 

And to kind of put that in terms, it’s easy to understand. If you think about back when I was playing sports, like you’d start to cramp, the first thing to do is like, oh, get a banana.

 

Yes.

 

Why? Because they’re high potassium.

 

Potassium.

 

And so when you’re cramping, they’re like feeding you a banana. You got to get your potassium up. This is the reason, as much as I hate to say, I don’t want to give University of Florida props for anything, but go dawgs.

 

That makes me feel better.

 

Go Tigers.

 

Oh Lord. Clemson. So if you look, that’s the reason they invented Gatorade.

 

Right.

 

Was to get those potassium levels up.

 

So we have football players cramping on the field. And so we’re going to give Lasix one to two hours out before running, depending on the route of administration. And like you talked about, we’re talking about dumping a massive amount of potassium.

 

And so right when you’re expected to go perform, your body is short on potassium. Muscle function is not going to be where it needs to be. One of the common things I hear from these horses that are running on Lasix is he just won’t fire.

 

Well, yeah, he won’t fire because we’re lacking the correct electrolytes in order to fire.

 

Yeah, you’ve got to find the balance of doing enough good to help with the bleeding, but not so much that we’re reducing our capacity to perform. Because to your point, it actually can be a bit performance limiting if you’re at a high dose.

 

And I mean, I found a thesis actually from a guy that really deep dived into the recovery effects of furosemide and some crazy stuff that’s happening when we’re at high doses, but at appropriate physiologic doses, because this was based off of like

 

the 250 and what we would essentially expect to get from that kind of dosage. It’s pretty wild how it can affect muscle recovery as well in these athletes if you’re overdosing it.

 

What was he seeing in that? So like, what would we consider that physiologic dose? And what would be, what kind of doses was he using?

 

So they were looking at, this was like an in vitro looking at muscle cells, because obviously in performance, when we’re pushing our body, our horses are pushing their bodies, same in people and animals, we’re breaking down those muscle fibers.

 

And then the rebuild of the muscle fibers is allowing us to be stronger and faster.

 

So he was looking at the different muscle cells and muscle regeneration, because we have what are called satellite cells in our muscles that essentially have yet to be differentiated, to go in and repair the parts that have essentially broken down in

 

terms of high performance. So he was looking at, it was 10 micrograms per mil, and then comparing that to 100 micrograms per mil. So he was taking it and 10-folding it.

 

And the 10 micrograms per mil came from the concentrations we were seeing in horses that were receiving that 250 milligram dose.

 

So 10 micrograms right in that, what we call a normal physiologic dose.

 

So he took that.

 

Let me do this. We talk in milligrams, but a lot of our listeners are dealing in milliliters. Lasix is going to be about 50 milligrams per mil, so a 250 milligram dose is going to be about 5 cc’s or 5 mls.

 

Right.

 

That’s why we had to take calculus to be a vet, so we can convert mils to cc’s.

 

It’s a big conversion, which is one mil is equal to one cc. But yeah, sorry, dad joke.

 

Oh, I’m here for it.

 

Go ahead.

 

I’m here for it.

 

All right, so let’s get back to it.

 

So we go from physiologic dose to like 10 times of physiologic dose. And what they were seeing is that in these in vitro cells, the amount of your satellite cells were the same. What’s the word I’m looking for.

 

Where these cells were sitting were the same. They were evenly distributed.

 

But the actual satellite cells were halted in their differentiation process, so they couldn’t actually get to the state of what we call myogenesis, or the creation of new muscle fibers. So they’re still there.

 

They’re still where they need to be, but they’re not able to actually complete their process to allow for the regrowth of muscle in that area if we’re at a higher dose. Now, I would have loved to see if we’re in the middle ground.

 

Like, at what point do we see that change? But that was the first study that I could find that had to do with the actual muscle recovery component because, you know, it’s kind of that argument, does it hinder muscle recovery? Does it not?

 

And it’s showing that at high doses, they were actually truly hindering it from this study that he’s done.

 

It’d be interesting to know, like you said, about, all right, we went from 10 to 100. It’d be really interesting to know if we could go in 10 microgram increments.

 

The other question, I think, that hasn’t been answered yet is what happens when we’re doing repeated doses? Right. You know, most thoroughbred horses, these horses are running, you know, every three to four weeks.

 

Some are running only every six weeks, but a three week, you know, a race every three weeks is a pretty stout schedule for a race horse.

 

But when we look at a lot of barrel horses, a lot of the EIPH in barrel horses, they’re running sometimes three days in a row. There’s sometimes some of these big super shows that may last a week. They could be running three to five times that week.

 

And I think there’s even some that they’re running more than once in a day.

 

Yes, definitely is.

 

And so then you add, we’re gonna, you know, some horses are running every week. Some are running twice a week. And so when you think about that, it’d be really interesting to know the compounding effects.

 

So they look at that in humans.

 

And I, for this podcast, I did not deep dive into the human repeated dosing, but they use this and they use it for hypertension, again, because we’re reducing that blood pressure.

 

They use it in cardiac failure because we need to keep that fluid out of the lungs.

 

But they’re actually showing in simple terms, because I came across it, that when we’re continually on furosemide, we’re actually having to increase our doses to get our effect.

 

Then we hit a point where it has a bit of a rebound effect, where we’ve got to switch to something else.

 

The receptor is basically what I’ve read in people become resistant to the effects of Lasix furosemide. It begs the question, that’s always a tough thing.

 

When we’re talking about horses, we always say of like a mice and men, I would say it’s Steinbeck, Steinbeckian of mice and men, because a lot of the things that we use was based on studies in people. But we have more, there’s just more funding.

 

There’s more money for the research in people, obviously.

 

Oh, for sure.

 

So we try to correlate the two. And the question is always, every time we try to do that, it seems like we find out like, yeah, that’s true, except in horses.

 

Yeah, that’s true.

 

And so it’d be really interesting to know those effects as well. So hopefully somebody will do that.

 

Well, and that’s funny. You say of mice and men, and some of the studies are in mice too. Yeah, all the studies are mice and men.

 

Mice and men.

 

That’s fair.

 

As well as we’re playing with Stein back here, you know.

 

One of the things that I thought was kind of interesting, and to be honest, I don’t remember if this was in one of the horse studies or one of the people studies, but it was actually talking about how we have some of these receptors in like a lot of

 

different tissues in our body. And I thought it was really cool that even in our red blood cells, we have like a similar transporter that actually causes like a chloride shift.

 

If it’s blocked, causes a chloride shift into the red blood cell, drawing some fluid into the red blood cell as well.

 

So we’re not, it’s not just all being excreted.

 

No. So we’ve got like, we’ve got about 95 percent that’s protein bound that gets into that kidney. But it’s getting into the kidney because it’s bound to that protein.

 

And it’s using that transporter. And then that other 5 to 10 percent is floating around and can mess with these receptors in other places as well, which potentially in our lungs can have a benefit. It stimulates prostaglandins as well.

 

And so we can, you know, encourage that vasodilation, but it’s actually drawing some fluid into our red blood cells too.

 

You know, the interesting question then would be, you know, if you’ve got increase in prostaglandins up and lower the blood pressure, what happens if some of these horses are actually running, and used to be in certain states, you can actually run race horses on a gram of bute. Some of the barrel horses are running on a little bit of an anti-inflammatory as well. The question is, is you have something that has, that inhibits prostaglandin, which one wins?

 

Yeah.

 

You know, which one wins?

 

That’s fair.

 

It’d be an interesting question to have somebody ask one day. Yeah.

 

So, you know, that’s the million dollar question is when we start using, you know, when you talk about the muscle development on these horses is, if we have a horse that is on Lasix, how often should they be running?

 

Because that’s a really valid question because one of the things I hear a lot is, you know, the first day of the show, running really well. Day two and three, they just don’t fire.

 

And the question then becomes, every time a horse exercises, no different than people, every time a horse exercises, and this is the same in people, we exercise, we compete, you get some level of damage. The body is going to get damaged in some way.

 

But the amazing part about the body is it can heal. It can heal quite rapidly. So the question then becomes, we’re running multiple days in a row.

 

If we don’t, one, we’re already, we’re already not having a lot of time between runs for that repair, but if we’re actually inhibiting that muscle repair as well, then the question is, well, this begs to say that this is why the later on in the show

 

for these horses are on Lasix, they’re just not firing the way they should. They’re just not running the way they should.

 

Well, not the doses we’re giving, the thesis that I came across, we shouldn’t be hitting that inhibition, if you will, of differentiation of those satellite cells, but it begs the question of, say we replenish our electrolytes, we do a really good

 

job rehydrating this horse, we make sure they get that potassium, that sodium back. Is that enough time for them to normalize, go through that repair cycle and then hit them with it again in the afternoon or the next day?

 

Because there’s really not, from what I could see, there’s not a lot that shows, okay, it takes you this long to then replenish that and recover because the time of action is fairly short and again, like in these thoroughbred horses, they’re not going to race back to back two days in a row.

 

Right.

 

And that’s where a lot of the research is.

 

Correct.

 

And you couple that with the compounding effects, what does, you know, if you’re giving that 250-milligram dose, but you’re doing it every day for three days, or if you’re doing it twice a day, does this have a compounding effect where we’re getting over that threshold of 10 micrograms.

 

Yeah.

 

So I think it’s, there’s a lot of questions.

 

Oh yeah.

 

And I think that’s why it’s taken us a while to get to this podcast because every time we dive into this, I feel like there’s more questions, or at least I have more questions.

 

I actually found an, I guess, it seemed too big to call it an article, but it’s like all the questions we have about furosemide and this guy goes into like, is more, I believe, from the human side of things, but and it didn’t answer all the questions I had.

 

No, it’s an older medication.

 

When you look at it, it’s been around a long time.

 

Yeah, there were studies in the 60s.

 

It was the first diuretic we ever had.

 

Yep.

 

But yet it seems like every time we turn around, we’ve got another question. So it’s quite interesting. So that begs to say, okay, if we are running on Lasix multiple days in a row, what do we need to be doing?

 

What are some thoughts that, or what are some things that we can do to try to minimize these effects?

 

Well, you’ve got to replace those electrolytes.

 

Absolutely.

 

And you’ve got to do that as soon as you can. Like the shorter we can make the time of being deficient in these, the better. Yes.

 

And hydrating that horse.

 

Right. And when you’re looking at electrolytes, that’s one of the things I tell people, you want a good quality electrolyte, try to avoid oxides, which most of your potassium in the form of potassium chloride are very easily absorbed.

 

Sodium, obviously, sodium chloride. Calcium, this is calcium carbonate is a great way to get that calcium replaced. So make sure you have a very good quality electrolyte with the right ingredients in it and make sure you’re giving enough of it.

 

You know, the great thing about the kidney too, is if you give them too much, now I caution this, don’t go out there and give like a five-gallon bucket of electrolyte to your horse.

 

Please don’t, please don’t.

 

But within reason, the body will regulate.

 

Oh, for sure.

 

The beauty of the kidney, it will regulate.

 

And I think it’s important to remember the timing of that electrolyte, not just after they run, but six, like I try to say, we need to probably give another dose six hours later, because we know the effects of furosemide is going to run four to six

 

hours. Well, if we’re given a ton of electrolyte, while furosemide is actively dumping electrolytes.

 

Then you’re not really giving electrolytes.

 

We’re just, like, we’re just, we’re just pushing them through.

 

Yeah.

 

So I do think a dose, you know, you can give a dose during that four-hour window.

 

Sure.

 

But really, I want to be post-six hours, given that next dose of electrolytes. And I’m also a big believer in, like, using a paste.

 

A few times, I’m, like, kind of funny about using a paste, because if you put it in the feed, now we’re hoping they eat it.

 

Yeah.

 

And hope’s not a plan.

 

So let me ask you this one, because I know a lot of people, even since I was young and working in barns, people like to give their horse Gatorade.

 

Yeah.

 

You like a Gatorade bucket? You don’t like a Gatorade bucket?

 

I mean, give a Gatorade bucket, but, I mean, let’s put this in perspective. You throw, you know, most people are throwing, like, a cup of Gatorade in the bucket. Yeah.

 

We just drank, like, a pint to a quart of Gatorade after a really good, you know, after a really good workout. All right. We’re 150, 200 pounds.

 

Yeah.

 

The horse is, like, 1,100.

 

Right.

 

So I think-

 

You gotta make that a concentrated Gatorade to actually get the value that you need.

 

So my thing is, like, use a good quality electrolyte paste and give it an appropriate dosage.

 

And I think that’s really important for these horses that are running on Lasix. We have to replace this.

 

Exactly.

 

The body does have stores. Like, that’s a great thing about the body. It’s got this stuff hid everywhere.

 

So as long as they’re eating, they can have some immediate recovery. But we’ve got to replace that, especially multiple days in a row, we’ve got to be heavy on the electrolytes.

 

Well, and to your point of the compounding effects and things that we aren’t fully sure of, then you also have to consider, how is this affecting our bones?

 

Because then we’re not just talking about immediate muscle recovery, but this is if it’s having a compounding effect and we’re messing with our electrolytes and we’re changing our shifts in calcium and things of that nature, there’s a lot more that

 

And that’s really important because especially when we find out the effects it was having on calcium as well, that is there for bone strength.

 

Exactly.

 

So when we’re looking at those compounding effects, multiple weekends, multiple doses a weekend, some of these horses may be getting it once to twice a week.

 

Right.

 

Like this could have, it could have potential, again, it’s one of those questions I have for somebody, what does that look like?

 

Maybe we need to nerd out on some more furosemide and figure out some of these things.

 

We need some nerds to dive in to this more, is what I’m saying.

 

Like, it’s a great topic because that’s been the hardest thing doing this podcast, is trying to find like guaranteed answers. We get asked these questions every week.

 

It’s a very difficult thing to answer because we don’t have some concrete that’s what we need to do, so we’re still navigating through this as well.

 

I’ve got a mentor from my last internship that is a respiratory genius, so I may reach out to him too, and just see if he’s got any references or contacts that are real experts on the Lasix deal.

 

Yeah, I’ve looked into it. It’s hard to find somebody that’s got all the answers, because again, we’re still waiting on these studies to be done. You know, another question I get asked a lot is like, okay, well, what can I use in place of Lasix?

 

And that’s a very difficult thing, because when you start looking, other diuretics don’t seem to have the same effect, like the trichlorpromazines, acetylzolamides. They’re not having the same effect of getting that volume down.

 

So Lasix still is our best choice. We’ve looked at some of the other medications. One was aminocaproic acid, helping to stabilize those capillaries and try to help out with it.

 

But it’s going to work more to help clotting. We don’t really need clotting. We need this not to happen in the first place.

 

Well, and the only other way, because there is technically one other way, is you could thicken the wall of your capillary by trying to lay down more collagen.

 

The problem with that is you need that barrier between your oxygen and your bloodstream. You need that to be, because we need that diffusion across that wall.

 

Right, without that diffusion, we don’t make it.

 

We can’t thicken the wall of our capillary, because that would be the only other way. Like the clotting, yeah, sure, is great, but you’ve still bled. You’ve just maybe bled less because you’ve clotted it.

 

Well, and like in people, there’s been a lot of work with nitrous oxide.

 

Yes.

 

And that’s going to function on that decreasing blood pressure through vasodilation.

 

Right.

 

That has not been showing as much promise in preventing this as we’d hoped.

 

One, it’s a tough delivery system. And it’s a very funny, it’s a very finicky delivery system. And that a little bit, you get vasodilation and life is good.

 

A lot. And your blood pressure tanks, you get it and you pass out.

 

Well, and my thought too, and this is just me probably spiraling into super nerd, is if when we perform at a high level and we’re exerting ourselves at a high level, vasoconstriction happens.

 

It’s probably important.

 

We probably need it. So if we vasodilate, like what does that do to our muscles? Like let’s say we don’t pass out.

 

Let’s say our blood pressure’s fine enough, but we are achieving a lower blood pressure solely through vasodilation, then are we actually getting blood to where it needs to be?

 

Are we getting too much blood to somewhere that it’s going, that it doesn’t need to be?

 

How are we changing the dynamics of performance and actually having nutrient delivery appropriate to the places that need it during a time of high physical exertion?

 

100%. I couldn’t agree more.

 

I don’t know how that would work. I don’t know all the details.

 

That’s the thing, because like I said, we are messing with the physiologic process here. And obviously the Almighty, he designed it in a way that it works.

 

And so when we start messing with it, we will always say like everything we do has a side effect. Every treatment we have has a side effect.

 

When we are using a medication, it’s basically saying that what we are treating is more important than the side effect we are causing.

 

That’s where the saying that y’all hear it all the time, surgery is trauma, medicine is poison, and alternatives of witchcraft, absent a diagnosis.

 

Which is why we focus so much on that diagnosis here, because then we can make a conscious decision that says, okay, the disease I’m treating, it’s more important to treat that disease than the side effect of this medication.

 

And every medication, I don’t care what it is, has a side effect.

 

Absolutely.

 

So again, it goes back to that whole, what is the side effect? What are we dealing with?

 

And again, we weigh this from an electrolyte basis, and we determine that we would rather have to correct this electrolyte issue than we would deal with hemorrhage in the lungs.

 

And I would say if people are using this on the track, and if we as track vets are administering this medication, then there is definitely a stronger benefit in preventing bleeding than the plus or minuses that could happen in other systems.

 

So, I think as far as EIPH goes, I think we tackled this. It’s a difficult topic.

 

We could do this all day.

 

It’s a very complex topic. We’re gonna probably have an EIPH round two at some point. See, I’ll listen for it.

 

But I like the end of everything with key takeaways.

 

Don’t use Lasix unless you know your horse needs it. Use it at appropriate doses. Understand that there are side effects that we need to counteract and create a balance for once we’re done running.

 

100%.

 

Couldn’t have said it better. So, again, if you don’t have a diagnosis, don’t use Lasix. Make sure this is an issue.

 

And a little bit of a cough is not a diagnosis.

 

That is, yes.

 

Yeah, I hear that all the time. Like, well, he coughed after a run, so he must be bleeding. Or you just came out of a dirt arena and there’s dust.

 

Yeah, sometimes I just cough walking through the hallway.

 

Yeah, so.

 

And again, try to catch it before you actually have blood in the nostril. There’s ways we can do that. So work with your veterinarian, try to get that accurate diagnosis, pay attention to your dosing, get a dosage from your vet, use it appropriately.

 

And then also understand once you give it, it’s now your responsibility to correct the things that happened.

 

Yeah, we gotta replenish that horse after.

 

Yep. So. Well, thank y’all for tuning in.

 

Thanks for sending the questions. We really appreciate it. April, thanks for filming this.

 

Kasey, thanks for editing and making this sound awesome. Thanks for our listeners out there. We really, really appreciate it.

 

If y’all got questions, keep sending them in. We’ve actually started a new thing on the podcast. When you send questions in, we’re trying to do some short video answers to them.

 

Just a little short, less than one minute clips. Because some of these questions that, you know, we get a ton of people asking questions, and the hardest thing in the world is to try to come up with a written response.

 

So we’re doing a little short video clips, so those will end up getting linked to the podcast. So if you have a question, maybe go check that link, and under that link, you may get your question answered. If you still have questions, send them in.

 

We’re doing our best to get them answered. We’re going to keep filming these, and hopefully keep changing the horse world one podcast at a time.

 

Yeah, keep giving us a reason to nerd out on something new.

 

Yeah, like I always say, I think I have as much fun doing this as I do about anything. It’s a lot of fun.

 

I think we all kind of dreaded digging in to the Lasix, but I got really into it last night. I’m not going to lie. This week, I’ve been having fun with it.

 

It’s like that whole thing, because it’s such a big topic.

 

You’re like, where do you start? And then when you start, you’re like, oh man, I just ended up in a rabbit hole and it’s 2 o’clock in the morning.

 

It’s kind of like a roller coaster. Like it’s a little overwhelming and then you’re on it and you’re like, wow, this is the coolest thing I’ve ever done.

 

Exactly. It’s a, being a nerd is great. So kids, if you’re listening, being a nerd, it’s pretty awesome.

 

Science is pretty cool.

 

Yeah, it’s pretty awesome.

 

So thanks again for tuning in. We look forward to seeing y’all next week. Take care.