Stenting for PAH?

[DarkProtonics]

Can PAH be treated by implanting a PTFE-coated stent that elutes sildenafil into the pulmonary artery? The stent immediately dilates the lumen, the sildenafil keeps it dilated, and the PTFE reduces the chances of restenosis.

A good theory, or am I coming up short again?

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[Trifling Jester]

Can PAH be treated by implanting a PTFE-coated stent that elutes sildenafil into the pulmonary artery? The stent immediately dilates the lumen, the sildenafil keeps it dilated, and the PTFE reduces the chances of restenosis.

A good theory, or am I coming up short again?

Similarly, we are pushing for more research into DES that elute nitric oxide directly into the ascending aorta. You have to find a really big stent though, obviously 3mm just won't cut it - you need to use the Mac Daddy stent. But, by your way of thinking, this would be doubly advantageous as it increases coronary perfusion and decreases peripheral pressures.

Future patent holder,
The Trifling Jester

 

[DarkProtonics]

Similarly, we are pushing for more research into DES that elute nitric oxide directly into the ascending aorta. You have to find a really big stent though, obviously 3mm just won't cut it - you need to use the Mac Daddy stent. But, by your way of thinking, this would be doubly advantageous as it increases coronary perfusion and decreases peripheral pressures.

Future patent holder,
The Trifling Jester

You could insert the catheter into the superior vena cava from the vena subclavia, thread it into the right atrium, through the tricuspid valve, make an upturn, pass the pulmonary valve, and then inflate the balloon to deploy the stent.

You'd need a custom-made introducer, catheter, balloon, and stent. Atrium Medical Corporation would probably be interested.

Maybe I could do this for my MD thesis --if I choose to attend a UK medical school and recieve an MBChB as my primary medical qualification--; that'd be worth an award or two.

Technically, I *could* legally use my OP as proof I had the idea first; be difficult, but doable; another career I was considering was law.

Any other comments or suggestions?

 

[radslooking]

Can PAH be treated by implanting a PTFE-coated stent that elutes sildenafil into the pulmonary artery? The stent immediately dilates the lumen, the sildenafil keeps it dilated, and the PTFE reduces the chances of restenosis.

A good theory, or am I coming up short again?

I don't know if this helps PAH, but it certainly will help the sex life in male patients.

 

[radslooking]

You could insert the catheter into the superior vena cava from the vena subclavia, thread it into the right atrium, through the tricuspid valve, make an upturn, pass the pulmonary valve, and then inflate the balloon to deploy the stent.

You'd need a custom-made introducer, catheter, balloon, and stent. Atrium Medical Corporation would probably be interested.

Maybe I could do this for my MD thesis --if I choose to attend a UK medical school and recieve an MBChB as my primary medical qualification--; that'd be worth an award or two.

Technically, I *could* legally use my OP as proof I had the idea first; be difficult, but doable; another career I was considering was law.

Any other comments or suggestions?

your original post won't mean jack. you have to patent anything you want done. until then, you have no legal rights.

 

[radslooking]

Similarly, we are pushing for more research into DES that elute nitric oxide directly into the ascending aorta. You have to find a really big stent though, obviously 3mm just won't cut it - you need to use the Mac Daddy stent. But, by your way of thinking, this would be doubly advantageous as it increases coronary perfusion and decreases peripheral pressures.

Future patent holder,
The Trifling Jester

what is the purpose of a huge DES in the ascending aorta eluting NO? For hypertension?

I can imagine that being a major problem when the patient becomes hypotensive. Or starts getting headaches.

 

[DarkProtonics]

what is the purpose of a huge DES in the ascending aorta eluting NO? For hypertension?

I can imagine that being a major problem when the patient becomes hypotensive. Or starts getting headaches.

Don't you know that *pulmonary* arterial hypertension can cause pulmonary hemorrhage, cor pulmonale, etc.? It's quite a bit more serious then systematic hypertension; http://www.mayoclinic.com/health/pulmonary-hypertension/DS00430/DSECTION=complications. It's usually treated w/ continuous infusion of epoprostenol directly into the pulmonary artery, inhaled illoprost, or oral sildenafil. My solution would eliminate having to carry a pump around all day, or having to use an inhaler 6x/day, as well as the administering sildenafil by the inefficient oral route.

And the DES is in the pulmonary artery, not the aorta.

 

[DarkProtonics]

your original post won't mean jack. you have to patent anything you want done. until then, you have no legal rights.

Actually, according to my lawyer uncle, if I need to prove I had the idea first, like if the PTO wants me to prove that when I file, or if the patent gets contested, yes I can use this.

 

[radslooking]

Don't you know that *pulmonary* arterial hypertension can cause pulmonary hemorrhage, cor pulmonale, etc.? It's quite a bit more serious then systematic hypertension; http://www.mayoclinic.com/health/pulmonary-hypertension/DS00430/DSECTION=complications. It's usually treated w/ continuous infusion of epoprostenol directly into the pulmonary artery, inhaled illoprost, or oral sildenafil. My solution would eliminate having to carry a pump around all day, or having to use an inhaler 6x/day, as well as the administering sildenafil by the inefficient oral route.

And the DES is in the pulmonary artery, not the aorta.

read what trifling jester suggested. I was responding to his suggestion of a stent in the ascending aorta. Yes, I know about all the other stuff you are talking about.

 

[DarkProtonics]

read what trifling jester suggested. I was responding to his suggestion of a stent in the ascending aorta. Yes, I know about all the other stuff you are talking about.

Oh, now I see. His suggestion is idiotic.

 

[BlackNDecker]

Oh, now I see. His suggestion is idiotic.

You have quite the sharp tongue, and apparently mandibular tachycardia...

The problem in Idiopathic Pulmonary Arterial Hypertension (IPAH) is proliferation of smooth muscle cells and endothelial cells througout the pulmonary vascular tree...not just in the large proximal pulmonary arteries. So a stent would dilate the proximal large artery, but would do nothing for the down stream arterioles which account for the lion's share of pulmonary vascular resistance, and therefore pulmonary pressure.

Furthermore, there are difficulties idiosyncratic to stents...not the least of which are the phenomona of restenosis and stent thromobsis. Stent thrombosis would be catastrophic in the setting of IPAH, most certainly requiring IMMEDIATE heart-lung bypass.

Furthermore, the patient population you would be inserting these stents into are very sick and often require ICU or CCU level care. By placing a drug eluting stent, you are committing these patients to a year of Plavix regardless of required future interventions...

Lastly, the plasma concentrations required for IV prostacyclins will likely not be achievable through a drug eluting stent.

I'm all for innovation, but these will certainly be difficult hurdles to overcome.

 

[DarkProtonics]

You have quite the sharp tongue, and apparently mandibular tachycardia...

The problem in Idiopathic Pulmonary Arterial Hypertension (IPAH) is proliferation of smooth muscle cells and endothelial cells througout the pulmonary vascular tree...not just in the large proximal pulmonary arteries. So a stent would dilate the proximal large artery, but would do nothing for the down stream arterioles which account for the lion's share of pulmonary vascular resistance, and therefore pulmonary pressure.

Furthermore, there are difficulties idiosyncratic to stents...not the least of which are the phenomona of restenosis and stent thromobsis. Stent thrombosis would be catastrophic in the setting of IPAH, most certainly requiring IMMEDIATE heart-lung bypass.

Furthermore, the patient population you would be inserting these stents into are very sick and often require ICU or CCU level care. By placing a drug eluting stent, you are committing these patients to a year of Plavix regardless of required future interventions...

Lastly, the plasma concentrations required for IV prostacyclins will likely not be achievable through a drug eluting stent.

I'm all for innovation, but these will certainly be difficult hurdles to overcome.

What about the DES eluting NO+oral sildenafil? And what's wrong w/ a year of clopidogrel...better than warfarin, right?

 

[JayneCobb]

What about the DES eluting NO+oral sildenafil? And what's wrong w/ a year of clopidogrel...better than warfarin, right?

There is currently a lot of research as far as duration of Plavix in DES stents, as we're finding that spontaneous stent thrombosis can occur at least up to 3 years out. So cardiac stenting is under a lot of scrutiny. Even bare metal stents isn't without issues. As already stated, the issue often tends to be smooth muscle hyperplasia, so all these treatments are going to be a finger in the dam until we aim our treatments at the underlying pathophysiology.

My aside, we're finding (not surprisingly - for further reading see House of God Law #13) that non-invasive management is more often than not better in the long term managment of medical conditions.

And please keep in mind, this is a professional forum and while we welcome all users, we ask that you please act like a professional and address other users as you'd like to be addressed.

 

[BlackNDecker]

What about the DES eluting NO+oral sildenafil? And what's wrong w/ a year of clopidogrel...better than warfarin, right?

I don't presume to know everything about IPAH...I actually had to brush up on it from Harrison's as it's not particularly common (however, we did have two IPAH patients in our CCU this month).

These patients are very very sick, and unfortunately are usually young. The interval from onset of symptoms to death is short and is reflective of our lack of effective medications. This really is not a disease amenable to stenting, because stenting would further aggravate the underlying pathophysiology: smooth muscle cell and endothelial cell proliferation. This is the basis of restenosis and the rationale for coating stents with cell cycle inhibitory drugs (cell cycle inhibition of endothelial cells).

The future of therapy in IPAH will most surely be biologics or genomics...i.e. monoclonal antibodies directed against the paracrine hormones and cytokines, or small inhibitors of mRNA which would inhibit translation of the paracrine hormones and cytokines responsible for smooth muscle cell and endothelial cell proliferation of the pulmonary vasculature.

 

[Trifling Jester]

what is the purpose of a huge DES in the ascending aorta eluting NO? For hypertension?

I can imagine that being a major problem when the patient becomes hypotensive. Or starts getting headaches.

I was being facetious. It was not to be taken seriously, just like the post I was responding to... Putting NO into the aorta would not lower peripheral pressures any more than a DES into the Pulmonary artery would treat PAH. It was a joke.

-The Trifling Jester

 

[DarkProtonics]

I was being facetious. It was not to be taken seriously, just like the post I was responding to... Putting NO into the aorta would not lower peripheral pressures any more than a DES into the Pulmonary artery would treat PAH. It was a joke.

-The Trifling Jester

What if the stent eluted epoprostenol AND sildenafil?

 

[JayneCobb]

What if the stent eluted epoprostenol AND sildenafil?

These are in all honestly probably idiotic proposals, epoprostenol aka flolan has an exceedingly short half life (minutes) and you could not put enough on the stent to last anytime at all. Both of these drugs tend to be effective for less than a few years before their efficacy wears off, and there really is only limited data on how treatment with these drugs affect the natrual history of PAH. All we can say is that there is some moderate improvement in exersise testing and other predictors but as far as I'm aware, there is little data which suggests these drugs actually prevent or amiliorate any of the long term sequela of PAH.

Again, if you're placing a stent, it needs to be impregnated with a material to combat the underlying pathophysiologic defect. The answer to PAH isn't any of the drugs you've listed, and even if they are, I'd be willing to bet that a stent with these drugs isn't going to be an effective answer.

 

[radslooking]

I was being facetious. It was not to be taken seriously, just like the post I was responding to... Putting NO into the aorta would not lower peripheral pressures any more than a DES into the Pulmonary artery would treat PAH. It was a joke.

-The Trifling Jester

damn you and your jokes. I want a sildenafil drug eluting stent put into my pudendal artery.

 

[aphistis]

damn you and your jokes. I want a sildenafil drug eluting stent put into my pudendal artery.

 

[BlackNDecker]

I want a sildenafil drug eluting stent put into my pudendal artery.

If you get a big/stiff enough stent you won't need the NO anymore

 

[howelljolly]

damn you and your jokes. I want a sildenafil drug eluting stent put into my pudendal artery.

Beat me to it.

 

[DarkProtonics]

These are in all honestly probably idiotic proposals, epoprostenol aka flolan has an exceedingly short half life (minutes) and you could not put enough on the stent to last anytime at all. Both of these drugs tend to be effective for less than a few years before their efficacy wears off, and there really is only limited data on how treatment with these drugs affect the natrual history of PAH. All we can say is that there is some moderate improvement in exersise testing and other predictors but as far as I'm aware, there is little data which suggests these drugs actually prevent or amiliorate any of the long term sequela of PAH.

Again, if you're placing a stent, it needs to be impregnated with a material to combat the underlying pathophysiologic defect. The answer to PAH isn't any of the drugs you've listed, and even if they are, I'd be willing to bet that a stent with these drugs isn't going to be an effective answer.

Perhaps we can coat the stent w/ eNOS, and make it actively keep the lumen open.

 

[JayneCobb]

Perhaps we can coat the stent w/ eNOS, and make it actively keep the lumen open.

If ifs and buts were hickory nuts, we'd all have a merry christmas.

 

[RTrain]

This all strikes me as rather cute. I know that sounds sort of patronizing, but I don't really mean it that way. When I was a pre-med, I thought I was going to be an oncologist, and I "invented" a targeted cancer therapy using my extremely limited (but over-eagerly sought) medical science knowledge. Then I got my dad (a university professor) to send it to a PhD researcher at the cancer center, who actually invited me to meet him in his office and very kindly and tolerantly endured my expounding on monoclonal antibodies and enzymatic degradation and who-knows-what-else. I feel sheepish now just thinking back on it.

Now fast forward 12 (!) years, and I'm doing something totally different with my life, and I feel pretty silly about my first "studies" in medicine, but I think it was a fun hobby and a good preparation for feeling enthusiastic about medicine. But DP, just remember that you are still very early in the process, and through no fault of your own, your understanding of pathophysiology and treatment principles is quite incomplete, and you won't be able to change that. You just can't self-teach basic medical sciences. So when we seem to think that your theories are simplistic and reflect a lack of understanding of cardiovascular medicine, it's because they are, and they do, but that's okay and normal.

Good luck.

 

[howelljolly]

When I was in high school I wanted to be a neurosurgeon. Now, surgery rounds is my idea of shifting dullness.

 

[DarkProtonics]

This all strikes me as rather cute. I know that sounds sort of patronizing, but I don't really mean it that way. When I was a pre-med, I thought I was going to be an oncologist, and I "invented" a targeted cancer therapy using my extremely limited (but over-eagerly sought) medical science knowledge. Then I got my dad (a university professor) to send it to a PhD researcher at the cancer center, who actually invited me to meet him in his office and very kindly and tolerantly endured my expounding on monoclonal antibodies and enzymatic degradation and who-knows-what-else. I feel sheepish now just thinking back on it.

Now fast forward 12 (!) years, and I'm doing something totally different with my life, and I feel pretty silly about my first "studies" in medicine, but I think it was a fun hobby and a good preparation for feeling enthusiastic about medicine. But DP, just remember that you are still very early in the process, and through no fault of your own, your understanding of pathophysiology and treatment principles is quite incomplete, and you won't be able to change that. You just can't self-teach basic medical sciences. So when we seem to think that your theories are simplistic and reflect a lack of understanding of cardiovascular medicine, it's because they are, and they do, but that's okay and normal.

Good luck.

That's okay. I wish to find people who will sit down and explain to me why I am wrong, rather than saying "you're so smart", or simply ignoring me.

 

[JayneCobb]

That's okay. I wish to find people who will sit down and explain to me why I am wrong, rather than saying "you're so smart", or simply ignoring me.

You've already been told above. Your ideas only treat the consequences of the problem and not the underlying cause. Like your thread on LVH, you don't treat the LVH, you treat the cause of the LVH like HTN. Your idea strikes me as being akin to stenting every cardiac cornary and then not placing the patient on a statin to treat the cholesterol.

 

[howelljolly]

Little buddy, noone is ignoring you. Youve got cardiology and critical care fellows on about a dozen threads that are discussing things with you. Normally when I ask questions to critical care fellows, they tell me to look it up and tell them about it tomorrow. When you ask a surgeon anything, the first question out of your mouth has to be "Doctor, may I ask a question?"

Theres an old saying "A little learning is a dangerous thing"

You're asking and proposing high level concepts, that with a bit more learning, or even a bit of common sense (which is sadly quite uncommon), you'll find are not such a good idea. A common trend in thoughts while countering your ideas seems to be "Ok thats great, but how are you physically going to do that?"

You only need to spend five minutes in a radiology suite to know that sending my patient with acute respiratory failure into an MRI with gad' is a bad idea. And its got nothing to do with the osmotic properties of gadolinium. Its got more to do with the pain you'll feel when the radiologist whips you with a lead apron.

A lot of us are happy to see someone thats passionate about medicine for the right reasons... so keep at it. And for pete's sake, dont whine.

 

[DarkProtonics]

Little buddy, noone is ignoring you. Youve got cardiology and critical care fellows on about a dozen threads that are discussing things with you. Normally when I ask questions to critical care fellows, they tell me to look it up and tell them about it tomorrow. When you ask a surgeon anything, the first question out of your mouth has to be "Doctor, may I ask a question?"

Theres an old saying "A little learning is a dangerous thing"

You're asking and proposing high level concepts, that with a bit more learning, or even a bit of common sense (which is sadly quite uncommon), you'll find are not such a good idea. A common trend in thoughts while countering your ideas seems to be "Ok thats great, but how are you physically going to do that?"

You only need to spend five minutes in a radiology suite to know that sending my patient with acute respiratory failure into an MRI with gad' is a bad idea. And its got nothing to do with the osmotic properties of gadolinium. Its got more to do with the pain you'll feel when the radiologist whips you with a lead apron.

A lot of us are happy to see someone thats passionate about medicine for the right reasons... so keep at it. And for pete's sake, dont whine.

I never said you all were ignoring me; I said other people were.

You guys are all excellent, excellent resources. I'd love to shadow a doctor, but no luck as of yet.

Basically, I either want to be an internist or a pathologist.

 

[howelljolly]

Well duh, of course other people will ignore you. Other people suck.

For now, watch those documentaries and reality shows on TV. Volunteer in a hospital, particularly in the ER or ICU. You wont get to do a blinkin' thing, but you'll see it. That should hold you over.

 

[DarkProtonics]

Little buddy, noone is ignoring you. Youve got cardiology and critical care fellows on about a dozen threads that are discussing things with you. Normally when I ask questions to critical care fellows, they tell me to look it up and tell them about it tomorrow. When you ask a surgeon anything, the first question out of your mouth has to be "Doctor, may I ask a question?"

Theres an old saying "A little learning is a dangerous thing"

You're asking and proposing high level concepts, that with a bit more learning, or even a bit of common sense (which is sadly quite uncommon), you'll find are not such a good idea. A common trend in thoughts while countering your ideas seems to be "Ok thats great, but how are you physically going to do that?"

You only need to spend five minutes in a radiology suite to know that sending my patient with acute respiratory failure into an MRI with gad' is a bad idea. And its got nothing to do with the osmotic properties of gadolinium. Its got more to do with the pain you'll feel when the radiologist whips you with a lead apron.

A lot of us are happy to see someone thats passionate about medicine for the right reasons... so keep at it. And for pete's sake, dont whine.

What are those "right reasons"?

 

[howelljolly]

An interest in medicine. Don't push it.

 

[J-Rad]

This thread reminds me of when I was a kid and thought I was going to build a computer, communications center, and a robot with my TI "Speak & Spell" just like the kid on some TV show...aah to be young again.

The answers to your questions, OP, have been fleshed out pretty well by the posters above. I would add: why a stent? If your looking to make a delivery mechanism closer to the affected vessels (which are at the arteriolar level) why not come up with a more benign vehicle (then you would also have to prove that your vehicle IS a more effective vehicle than the traditional routes of administration)?. Stenting the main pulmonary artery (MPA) gets you nothing; in someone with normal anatomy the main PA was never stenosed (narrow) to begin with so widening the MPA would gain you nothing downstream (as others have already stated). In fact, I could make an educated guess that increased flow could exacerbate the condtion and potentially put someone into pulmonary hypertensive crisis. Remember there are plenty of adults and children that have non-idiopathic pulmonary hypertension due to increased flow states into the lungs (VSD, ASD, hypoplastic left heart). In fact, in the congenital world we sometimes band or lop off the main PA to control pulmonary flow. So I can't see how implanting a stent (and it has to be dilated to stay in place) would help pulmonary hypertension. The stent in the large vessel carries the risk of vessel rupture or intimal tear and going to the cath lab has risks in and of itself (sedation a/o general anesthesia, placement of catheters and sheaths, arrythmias due to the catheters in the heart). And this is a little bit of speculation on my part, but I would guess that very few adult interventional cardiologists stent the great vessels (vs. the coronaries they're always going after). Pediatric interventionalists are stenting vessels of all sizes (except for coronaries for the most part) in children and adults, and would probably be your go-to people to do your proposed procedure-thus (entirely theoretically I admit) potentially limiting your pool of docs to do your procedure.

 

[howelljolly]

Funny... you reminded me that I applied to med school with the intention of becoming a peds cardiologist. Then I discovered that I'm too stupid.