Angiogenesis a bypass

[Max_123]

My father has blocked arteries, but it appears there is adequate blood flow around a completely blocked left-side large vessel.of the heart.  I'm concerned and interested because this may happen to me so I have done some reading on the subject.  I read angiogenesis is the process and posts on this forum indicate the process is collateral vessel?  Thank you in advance.:)

[kenkeith]

Yes, there is a difference.  Angiogenesis is the development of small vessels mostly small arterioles, capillaries and venules. It has a connection to generate small vessels from epithelium cells (lines the vessel), blood flow, etc.  Angiogenesis happens as an example from a wound.  Out of control, it can be cancerous tumor.

But when an exsisting artery is occluded  the development of blood flow from existing collaterals may be activated.  There is evidence, mechanisms leading to the development of collaterals capable of conducting blood efficieniently differs from those usually involved in angiogenesis.  I have read arteriogenesis is "state of art"  term that includes both angiogeneis and collateral growth recognizing the difference between the two processes.

If you have other questions...what has been stated is not very much detail, and I hope it is not confusing!

[Max_123]

Is there any physiological basis that can be relied on to develop collateral vessel bypass?  It seems some people or at least most people that have heart issues have stents or by-pass.  The short answer may be people that have a natural bypass don't participate on health forums as they don't have a heart a problem.  Are there autopsy reports or something?  I read autopsy reports state military personnel autopsies showed significant blockage in many young people!  No mention of any natural bypass.

[ed34]

The development of collaterals doesn't occur in everyone. During one of my many stays in hospital, I was talking to a man who had a 95% occlusion in his LAD but no collaterals were forming. His Cariologist told him that the collaterals don't seem to always form in people and this is why it is still believed by some experts to have a genetic element. Collaterals are good if they form in that they can keep heart tissue alive. However, in many people they only provide enough Oxygen backup to be at rest or very slight exertion. So many people have the luxury of collaterals keeping them alive until a better solution can be decided.
I am still unsure what effect on collaterals a bypass or stent has. How does the increase in pressure in the LAD affect these newly formed vessels and the vessel providing them. Surely back pressure will be created. Collaterals in the bottom of my LAD were pushing blood UP the vessel and keeping me alive. However, now my LAD is fully patent, and high pressure is pushing DOWN the LAD, how is this affecting other vessels in my heart through the collaterals. I have an outpatients appointment with my cardiologist soon, I will ask him such questions and let everyone know. I also have a working Lima grafted to the LAD and this must also play around with pressure/flow as blood also streams in through the left main stem.

[kenkeith]

Max, if I understand your question,  you are asking if there are any attributes or identifiable characteristics that are reliable to predict if one will have collaterals for their blocked vessels.
No, there is no way to know prior.  If your father has CAD, and collateral blood flow and you are concerned there may a genetic component for CAD, you need to take precautionary measures to prevent CAD such as control your cholesterol, blood pressure, proper diet, exercise, etc.

However, my notes on the subject  from a few years ago indicate there is evidence why some people with diabetes do not have adequate blood supplying collaterals.  There is a biological component associated with diabetes and the cardiovascular system.... and my notes indicate there is evidence supported by lab experiments and general knowledge of fluid dynamics (or hemodynamics) that more than one occlusion in the same vessel prevents an adequate flow of blood from collaterals....may require interventional therapy.

[kenkeith]

This a Cleveland Clinic  doctor's response:  Stents, if patent, are likely to decrease collateral flow to the arteries in which they are in, thye will not affect distant arteries.  This is not a problme because forward flow (throught the stent) and collateral flow are both driven by a pressure difference, so as long as there is forward flow, the collateral flow is no longer necessary.  Again, stents do not inhibit collateral flow to the unstented arteries.  EECP is done to alleviate chest pain from disease in arteries that are still diseased (unstented), therefore it is not contraindicated.  Finally, stents have struts in them so they do not cover the openings of the diagonals, thereby, permitting continuous flow to those segements.

>>>I agree with the doctor's post  [except some spellings] :)  I will go into detail from my years of researched notes and prior forum posts to answer your questions.  This is Max's thread, and I will wait to see if he has any questions first!

[ed34]

Thank you for that information kenkeith, much appreciated. Do you know what happens with regards to my Lima pumping blood into the LAD along with the flow through the main left stem? I assume that there shouldn't be a problem because the LAD will only accept the flow/pressure it requires?

Thanks again :)

[Max_123]

No one has ever stated collaterals develop with everyone from what I have read on this forum.  What has been said is that everyone has collateral vessels and the focus of this discussion it seems to me should be what underpinnings open and remodel collateral vessels for people with CAD or development after an acute myocardium infarction.  I spent some time searching the internet regarding collaterals and found nothing that reports anything other than everyone has collateral vessels.

Ed, how do we know what you describe actually occurred?  Could be a mistake!.  Maybe if you start a thread someone can help you that had a similar experience.  I would like to know more about what causes collaterals to develop and if there is anything I can do now because my father has CAD and I understand there is a genetic factor for CAD that can occur to a person at a young age. I wouldn't like to have my chest cracked open.  Thank you in advance.  Maybe I should have titled my post "collateral bypass" and not "angiogenesis bypass"; that seems to be irrelavant.

[ed34]

well max these things are determined and witnessed by a history of angiograms.
In my case, in Feb 07 there was a 90% occlusion in the top of my LAD and small vessels were seen on the Angiogram grouping around the base of the LAD. I had very bad angina at that time, but stenting a blockage in the mid circumflex cured that. No
collaterals were seen trying to feed the circumflex.
In aug 07 I suddenly felt very strong bouts of angina and was admitted back into hospital because they included chest pains. A new angiogram showed that the LAD was 100% blocked at the top and the group of vessels gathered at the bottom of the LAD had now anatomised to it, giving it a small feed. The feed was very small indeed and just enough to keep the heart tissue alive when at rest. A bypass was then performed and three months this failed as the 2 veins closed up. Strangely enough the collaterals hadn't receeded, which is a good thing because otherwise I would likely have died. They were still there as a backup and feeding into the LAD. I don't know how long they stay in place but they are still there two years later. Now my LAD is fully opened, it will be interesting to see what happens to those collaterals in the future.

[kenkeith]

Hi Max, you are doing the right thing by learning as much as you can about heart disorders...I have found it very helpful to decrease anxiety, apprehension, and it does motivate to exercise, maintain a healthful diet, etc.

I will depend on my notes going back several years and it hasn't been updated with current information, if any, on the subject (collateral vessels), as I have felt the issues are settled. It seems stress induced vessel remodeling (change in size, development) is altered by pathological conditions such as diabetes, hypertension and artherosclerosis (hardening of vessels).

Now, my take and certainly open for discussion as no one has all information, and starting with the facts that are not professionally disputed.  It is recognized that gradient pressure is perfusion force "F" and resistance "R" times blood flow "B" are directly proportional to F.  R is the resistence due to fluid shear stress (friction of blood flow against vessel walls) and B blood flow...both R and B are low when conduction through a healthy vessel is not impeded.

We analyze a segment from the opening "a" to "b" the end of the segment. When the vessel (segment a to b) becomes occluded,  R increases and that is directly proportional to F causing an increase of perfusion force across the gradient....this the beginning of a single-vessel blockage.  As the occlusion increases, the diameter of the vessel decreases and F increases until F overcomes the resistence of the smaller collateral vessels.  As F increases B (blood flow) will increase and collateral vessels will provide sufficient blood supply, and probably no heart issue is every known.  

Now consider a second occlusion begins downstream in segment a to b. This will change  the  fluid dynamics within the segment of the upstream collaterals that is proportional to the driving pressure (ie, the pressure gradient) between these 2 points a and b.  After occlusion, a pressure gradient between the upstream and the downstream part of the segment results in increased blood flow in the collateral network. However, because this blood pressure gradient is limited by the resistance vessels lying downstream of the occlusion, and is further diminished as collateral flow increases, the remodeling of the collateral vessels is restrained. This would explain why only about  40% of the maximal physiological conductance is restored after arterial occlusion....May require intervention with two or occlusions even if there is some collateral flow.. It is my understanding collateral flow is not picked up with an angiogram until there is 99to 100% blockage.

**""An experiment developed by Eitenmüller and colleagues associated both femoral occlusion and femoral arteriovenous fistula, bypassing that downstream resistance arteries. The pressure gradient between the upstream and downstream segments of the occluded femoral was therefore quite significant, representing 60 to 70 mm Hg, driving a pronounced increase in collateral artery blood flow. The authors used this clever surgical model to demonstrate downstream resistance arteries to demonstrate that higher blood flow in collaterals results in more extensive remodeling such that maximal limb conductance reaches normal values or is even surpassed. This experimental process could be compared with events occurring during muscular exercise: there are several lines of evidences suggesting that the molecular mechanism of exercise-induced upregulation of vascular eNOS expression are closely related to the changes in fluid shear stress in the vasculature. Exercise increases heart rate, which in turn increases blood flow and vascular shear stress, leading to enhanced NO production".      May help explain why exercise is helpful and when a cardiologist decides to stent or bypass procedure for multi-vessel occlusions and not to open an occluded vessel with good collateral blood flow.

Sorry for the long explanation....and that is the skinny on the subject. :)

[Max_123]

Thanks for your time.  To understand and referring to the model (segment 'a' to point 'b', and occlusion1 and occlusion2), if occlusion 2 (downstream lesion) is stented, that will increase collateral flow from occlusion1, and if occlusion1 is stented, that will regress collateral flow!!  If that is true, my father's collaterals will be sufficient if there is no blockage down stream. Would that be correct? .

[HeartTwo]

I am not associated with the medical profession however, I have read many, many papers and studies on the subject matter and, have had 4x CABG in July 2008. Once again in my lifetime I consider myself to be among the luckiest of lucky.  My understanding is that everyone does not grow collateral arteries around their blockage. Furthermore, "Expert Reviews" suggests . . . "transferring the promising experimantal results into clinical practice has been more cumbersome than initially anticipated"  Several of the papers I have read refeer[sp] to this process as fluid dynamics. Point A to point B. At point B a blockage has developed @ 100%. Fluid continues to flow in the direction of point B in which the artery begins to develop a collateral. To determine the size and magnitude of the collateral(s),  testing must take place.
In my case, my EF remained within normal range. My first cardiac catherization revealed "a lot of collaterals" back in 1995. I clearly had CAD.
I am going to go back to the lab's who performed the testing and get copies of the test notes to check what exactly my EF was.

[kenkeith]

It is my understanding the vessels (can be microvessels as well) are in place and remodel (develop) based on hemo dynamics or fluid dynamics if you chose.

[HeartTwo]

Had Nuclear Imaging Study - Exercise Stress about 3 weeks prior to 4x CABG. Went and received the results yesterday. My EF was 60% !
Ok, so now luck is my new best friend. My opinion is that I attribute this to my body developing collateral arteries over a period of 30 to 40 years. First detected in 1995, these 'collaterals" continued to grow at a pace > my arteries deterioration. I was very active and had almost NO symptoms. These collaterals suplied more than sufficient blood as is evidenced by the EF of 60% just prior to my CABG.
Interesting to note that I had conversations last night with over 50 years of medical experience of the BSRN, BS, MS RN type and,opinions seemed to be scattered all over the place. Is there a reader out there who would argue against me having CAD and Ischemic Heart Disease? I appreciate your input. Thank You.  

[kenkeith]

I experienced the same phenomonon over a period of years....Not everyone seems to be a good candidate and that appears to be diabetics (vascular disease), and aging individuals who may have some hardening of the vessels and loss of flexibility of vessel walls.  My thoughts are as a vessel begins to occlude, hemodynamics (arterial pressure, blood flow velocity increases, etc.) begins to remodel vessels  and has the occlusion increases so does the hemodynamics.

My theory has been when there is medication and/or stents to treat CAD the hemodynamics change and the system does not see an occlusion problem to react. I have read there is a school of thought that does not agree.

[ed34]

"My thoughts are as a vessel begins to occlude, hemodynamics (arterial pressure, blood flow velocity increases, etc.) begins to remodel vessels  and has the occlusion increases so does the hemodynamics. "

I find it hard to swallow this, not that I'm arguing with expert, but simply that I can't see any plain logic in it. I have seen patients with no collateral developement who are in their 40's and without diabetes, I wouldn't class these as old. I was 46 when collaterals were seen forming so I assume that the age limitation factor much be further upstream.
My real struggle with this idea is that blood pressure is high in many patients who develop CAD and it has been high for many years. So if blood pressure was an issue, one would expect to see everyone develop collaterals (in my opinion anyway). Flow velocity is really going to achieve nothing because it's the pressure which matters.
What intrigues me is that according to my history of angiograms, my collaterals started to form when I began experiencing angina discomforts. I still cant help but wonder whether a chemical process triggers collaterals to begin forming. Has research been done for example to see what happens when collaterals (undeveloped) sense the presence of Troponin I ?

[kenkeith]

QUOTE: "My real struggle with this idea is that blood pressure is high in many patients who develop CAD and it has been high for many years. So if blood pressure was an issue, one would expect to see everyone develop collaterals (in my opinion anyway). Flow velocity is really going to achieve nothing because it's the pressure which matters".

>>>>I don't have the knowledge of molecular science related to the anatomy of arteries, nor the a complete understanding of the physics  related to hemodynamics as that also involves neurohormones in the blood that is a chemical mediator, etc., etc.  

But one cannot dismiss velocity when referring to hemodynamics. For reference the study of the causes of motion is called "dynamics" and that would include  "dynamical" variables: momentum, force, potential energy, pressure and power. Each of these quantities will directly or indirectly involve the mass of the object.  Mass is defined dynamically in terms of force and acceleration (velocity).

Start with anastomosis: When blood vessels connect to form a region of diffuse vascular supply it is called an anastomosis (pl. anastomoses). Anastomoses provide critical alternative routes for blood to flow in case of blockages.  

Then understandingly, force (pressure) is required to change momentum; alternatively, a change of momentum ("impulse") causes a force to be felt.  Since momentum has dimensions of mass times velocity, force has dimensions of mass times acceleration.  But  not all of that energy goes into moving the blood. Some of it is stored as potential energy in the increased blood pressure, some is stored as elastic energy in the walls of the vessel (inner lining of vessel),  and some is lost to dissipation. Regarding the age that would more accurately refer anatomically and not chronologically, and age can break down the inner lining and a loss of elasticity.  This would inhibit vessel remodeling.

As you know hemodynamics also involves macroscopic turbulence (You may know about turbulance of the major vessels and its significance) for anastomosis . But the relevant turbulance are eddies (smaller turbulance)  This is due to the assumption that viscous dissipation is proportional to the velocity gradient.  I don't believe one can dismiss velocity any more than any other factor for hemodynamics.

[ed34]

After doing some more research in EECP, I think I am getting a bit closer to understanding why collaterals form. EECP simply opens existing arteries and it isn't the pressure/flow or mass that creates collateral growth, I read this....

"There is preliminary data suggesting that EECP can help induce the formation of collateral vessels in the coronary artery tree, by stimulating the release of nitric oxide and other growth factors within the coronary arteries. "

So, it looks as though certain chemicals are required which excite the collaterals into developing which makes much more sense to me.

[kenkeith]

I agree with what you have stated except your conclusion is partially incorrect.  To add what has been said, collateral arteriolgenesis starts with endothelium cells (inner most cells that line the vessel),  but it is the physical forces that is the primary stimuli.  It is FLOW that increases size, and PRESSURE determines wall thickness of the vessel and are the mechanisms of transduction of the mechanical stimulus into collateral vessel growth  response (don't confuse angiogenesis growth factors with arteriogenesis, arteriogenesis has another dimension).  This in part is the basis of my theory that a stent implant inhibits collateral growth because there is damage to the endothelium cells and smooth muscle mitosis is affected as well.  And when the stent dilates the vessel that will also affect the pressure and velocity of blood flow. And studies have identified a host molecules whose endothelium production is mediated by shear stress (velocity).  That may be what you are referring to (NO, growth factors, etc), but velocity is the stimulus and the variable factor.  EECP increases pressure, pressure increase velocity, and velocity increase shear stress.

It is known blood flow velocity is inversely related to the cube of the collateral  vessel radius...so increased blood flow (velocity) directly results in an increase shear stress.  Since growth increases collateral vessel diameter, shear stress falls quickly.  This maybe the reason ateriogenesis stops prematurely and restores only 35-40% of the maximal condition of the replaced artery.  Also, large vessels with low blood flow tend to close or reduce their lumen (vessel channel), but small vessels with chronically (possibly years) increased flow tend
to get wider.

[Max_123]

QUOTE: "My real struggle with this idea is that blood pressure is high in many patients who develop CAD and it has been high for many years. So if blood pressure was an issue, one would expect to see everyone develop collaterals (in my opinion anyway). Flow velocity is really going to achieve nothing because it's the pressure which matters"
_________________________________________________________

Thanks kenkeith to take your time to answer questions.  Pressure between segment A-B is not systemic pressure, and it is clear to me what has been said regarding arterial pressure, and it is that pressure that opens or increases blood flow in the already established microvessels and any other vessel available.  Flow velocity, shear stress, endothelium cells, etc. (velocity) is not going to achieve anything is an ignorant conclusion. The elements are all intricately involved for cardiovascular maintenence, etc.

QUOTE: "Also, large vessels with low blood flow tend to close or reduce their lumen (vessel channel), but small vessels with chronically occluded (possibly years) increased flow tend to get wider"

Answer: For consideration, I believe vessels do not need to be chronically occluded before there is remodeling.  I have read acutely occluded vessels have induced remodeling of vessels and have saved heart tissue during an MI.  Thanks again.

QUOTE:HeartTwo:Is there a reader out there who would argue against me having CAD and Ischemic Heart Disease? I appreciate your input. Thank You.  

Answer: How can anyone argue against you having CAD and Ischemic heart disease when you have stated you have had 4x CABG.  Are you suggesting you may not have had occlusions and the by-pass was unnecessary?

.

[kenkeith]

Max quote: "For consideration, I believe vessels do not need to be chronically occluded before there is remodeling.  I have read acutely occluded vessels have induced remodeling of vessels and have saved heart tissue during an MI.  Thanks again".

Do you have a source for acutely occluded vessels developing collaterals? Thanks.

[RogerInTexas]

This is a fascinating discussion.  I have (or at least had) CAD.  I ran for 30 years.  In 2001 I experienced a frightening syncopation of my pulse (arrhythmia) and, after tests and procedures, underwent 5XCABG plus a left carotid endarterectomy.  This got my attention, and I radically changed my diet.  As of this week no further visible occlusion has occurred.  I have tried to educate myself about heart disease since my bypass, and had I known then what I know now I'd have refused the surgery, with its attendant risks.

My cardiologist informed me that, without collaterals, I would have suffered angina and eventually collapsed as the arteries closed completely.  As it was, I ran several miles the day before my surgery, albeit with some difficulty.  After the surgery I had far less difficulty running, to be sure, but I could have done without it at that time with almost no other diminution of my life quality.

I continue to believe that the "trigger factor" for collateral development is aerobic exercise of a sufficient level.  All of us have the latent vessels, and certainly the factors enumerated by Kenkeith are valid, but I believe exercise is the factor almost no one discussed, but that is essential to foment their development.  

To me the process is quite simple:  Bad dietary habits produce plaque in the arteries, even if one exercises (see Jim Fixx).  Occlusion(s) occur.  Exercise increases the F factor (perfusion pressure)  Fluid dynamics explains why the collaterals are developed.  And life continues, with some loss of physical capability.  One can do several things about this:  Nothing, surgery, stent(s), angioplasty, chemicals, dietary change, reduce arterial inflammation, or some combination of these actions.  Most patients will do whatever their cardiologist recommends, as I did.  

Some day someone (not the major drug companies, who love things the way they are) will develop a process whereby plaque can safely be removed from arteries, and this issue will become moot.  But most of us will be long gone by then.  Mainstream medicine still buys and peddles the lipid hypothesis, even though it's been largely discredited by many studies and physicians (Eades, Kendrick, Masterjohn, Taubes, among many others).  Studies such as JUPITER are a sham and a farce, funded by and promulgated for the pharmaceutical industry.  Alternative approaches to healing are sneered at, and studies of these approaches are never funded.  Virtually all elective admissions to hospitals today are the direct result of bad dietary habits and/or self-abuse or self-neglect.  This will probably never change, regardless of what healthcare "reforms" are passed.  

So it's up to the individual to educate him/herself and take charge of his/her health.  This forum certainly attracts those people.  I'm glad I found it.

[ed34]

Exercise does seem to make a lot of sense. It's as if you reach a certain level of fitness and the body knows it has to maintain that level as much as possible. If you do nothing, and your heart is fine at rest, then perhaps this is the key to not developing collaterals.
I had been working in the building trade for a few years when I had to have my first stent and collaterals were noticed. I had been digging 3 metre deep trenches with a shovel and mixing tons of concrete by hand with no real issues. All that was with a 100% blockage in the LAD. If I had a desk job, maybe the collaterals would not have grown.
Perhaps demand is a major key.
I too believe that if I had not accepted beta blockers after my first stent and went straight back to work, I would have been fine. Since having 5 more stents and a triple bypass I feel a lot worse. I have thought about exercising a lot more but the discomfort gets too much very quickly so I'm in a catch 22. I can't exercise enough to grow any more collaterals and without them I can't exercise. Any ideas on how I might be able to get around that one? I've tried working through the discomfort but it really is impossible, I'm gasping for air, clutching my chest and feeling terrible pain in my throat.

[erijon]

Qoute:
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Some day someone (not the major drug companies, who love things the way they are) will develop a process whereby plaque can safely be removed from arteries, and this issue will become moot.  But most of us will be long gone by then.  Mainstream medicine still buys and peddles the lipid hypothesis, even though it's been largely discredited by many studies and physicians (Eades, Kendrick, Masterjohn, Taubes, among many others).  Studies such as JUPITER are a sham and a farce, funded by and promulgated for the pharmaceutical industry.  Alternative approaches to healing are sneered at, and studies of these approaches are never funded.  Virtually all elective admissions to hospitals today are the direct result of bad dietary habits and/or self-abuse or self-neglect.  This will probably never change, regardless of what healthcare "reforms" are passed.
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I couldn't disagree with this statement more.  I would ask you the same thing I ask everyone that makes this statement. Given what is known, would you be better off with a total cholesterol over 300 or under 200 as recommended? Of course, less is better, how low is the question open to debate. You make a fairly condemning statement about current treatment options but don't mention what your levels were prior to your surgery.

There is no reason to believe that the JUPITER study was flawed unless you want to implicate the FDA and The National Institute of Health both of which were also involved in the tracking of results as well as the funding. Even if JUPITER was flawed, there are many other studies that outline the benefits of statin therapies. I hear this so often but no one can ever show anything to back up the position that these trials were compromised, just conjecture.

One thing we do agree on is that people need to take responsibility for their own health, eat healthy and exercise. That would go far towards resolving this whole issue.

Jon

[ed34]

"I couldn't disagree with this statement more."

I have an open mind on such issues because large sums of money make their way into many circles and affect lots of decision making people. In the UK health experts were telling the government for decades to concentrate on fighting the smoking habit in the general public. The government of course didn't want to listen because millions of pounds in taxes were gained every year in taxes from cigarettes. They agreed in the end to print warnings on the packets. Europe was far ahead, they had banned smoking in public places and educating children about the dangers of smoking. Health experts tried every way they could to convince the government but the problem was the tax gains. Even money spent in the health system on smoking related illnesses couldn't be used to persuade the government. 4 billion pounds is spent each year on smoking related illnesses, but smokers were paying 8 billion pounds a year in taxes on cigarettes. They were paying for their own treatment, plus the treatment of nearly everyone else who didn't smoke. It was only when the public began to be educated through leaflets etc that the changes occurred. The public became aware of what was going on and the government had no choice but to align us with Europe. We suddenly had cigarettes shoot up in price, public smoking bans and even fines if someone throws a butt on the floor in the street. Smoking has reduced a lot in the UK now, but the tax loss has to come from somewhere. It will come from proposals regarding global warming. We will all have to abide by a carbon footprint and pay taxes for anything over that limit. The UK accounts for less than 2% of carbon emissions in the world, yet our government claims we must show the way and set the example. Just excuses for the new set of taxes.
So if cigarettes have been so political, I see no reason why other drugs can't be in the same situation.
How much research is actually vetted? If a large company says it took a sample of 100,000 patients and carried out research, who spends a lot of money on checking that the research really took place? Or more importantly that the data has been given correctly and not manipulated? The only people who can afford such research are the drug companies themselves, will they produce results saying statins do not really work?
Everytime a Doctor or anyone stands up and says they don't seem to be doing anything to their patients, the big drug companies simply stand up and say "listen small fry, we have research which says it works for 100,000 people, so dont make yourself look silly, sit back down".
Like I said I have an open mind on this and especially with the way the economy is unbalanced at the moment, I wouldn't be surprised at anything.