Pierre:
Your question is why should EECP stimulate collateralization?... Here are a few comments I would like to make, to explain why improve collateralization is most likely the cause of improvement in EECP treated patients. I will be here more sepcific and use medical terms. Here it is. My first question is:
IS IMPROVED COLLATERALIZATION THE CAUSE OF THE BENEFITS SEEN IN EECP TREATED PATIENTS?
I personally have NO other explanation. The thallium imaging improvement showed in EECP treated patients, as described in previous publications, is hard to explain otherwise. Of course you could say that EECP improves the coronary blockages themselves,... but here that is much more difficult to explain pathophysiologically. On the other hand, that latter explanation would be great!... but I rather beleive that collateralization improvement is the cause of the improvement.... now for the second question:
WHAT IS THE CAUSE OF IMPROVED, PERSISTENT, COLLATERALIZATION?
I agree with you that there are no definite proof of that, and that the pathophysiological mechanisms have not been elucidated. In biology and medicine, most everything has a "humoral explatation" with various mediators exercising their influences of neighbouring cells, creating a VERY complex broth in which these cells are living. Cells are in fact often exposed to factors that exercise agonist and antagonist actions. Furthermore, cells will "obey" to these factors, only if other factors are favoring the response, and are not inhibiting it. Molecular biology is the great tool which allow researchers to elucidate which of those mediators is the most influential, at that perticular site, and at a specific moment.
For collaterals, a lot has been done. I am a little bit familiar with that, but not an expert. Anyhow that is what I understand. Collateral vessels are present in all of us, but grow a lot, in the heart, when we have a blockage which appear in a coronary artery. The growth of these collateral appears to be due to "growth factors", which appear to be triggered by the lack of blood flow to an area of myocardium. These growth factors have not been elucidated. Hypotheses have been that local nerves may be at play (as a local axon reflex), and those allow the message to be given to the collaterals to grow. Another hypotheses is that the upstream transmission is through the smooth muscles of the collateral vessel wall itself).... All of the above, to me, is an intelectual talk which has no answers,... and is irrelevant to the action of EECP at this point of time. Afterall, we want to know, as clinician and investors, whether EECP is a good treatment modality or not. (When ehter anesthesia was invented, around Boston if I am right (MIT), I am not sure that they had elucidated the exact mechanism of action).
OK... one has to agree that collateral flow IS increased DURING EECP treatment: that is, in my view, NOT debatable. Coronary blood flow has been demonstraed to be increased by 2 research groups (abstracts) during EECP treaement, and when coronary flow is incresed, collateral flow HAS to be increased. You see ...(an explanation for non-clinician)... EECP increases DIASTOLIC pressure, and this is the time when coronary arteries are pefused... We know that there is no blood flow during SYSTOLE (the cardiac contraction) because the heart muscle squeezes blood out of its chambers, but also squeezes itself, as a sponge, thereby preventing blood perfusion to itself...
We know therefore that coronary perfusion is a DIASTOLIC phenomenon. EECP increases, guess what, DIASTOLIC PRESSURE... and may have the best benefit in patients treated for angina because some of these medications decrease diastolic pressure (normal diastolic pressure is about 60-90)... and if one of your patient has, let's say 50 mmHg of diastolic pressure, and that EECP improves that to 90... the net result is marked improvement of coronary perfusion....no doubt! (See your IABP experience that you cite).
And that is the crux of the story because we know (for sure!) that collaterals are weak vessels... that only stay open if the flow through them is increased... otherwise, they will collapse...(Oh! Nooo!)... CONCLUSION: EECP improves collateral flow DURING the treatment istself... I don't see why it would not.
Now for the PERSISTENT effect: once the collateral system has been more open, with improved flow for 1 hour at a time, local regulatory mechanisms probably trigger a form of angiogenesis (vessel growth), which leads to an visible increase size of the collateral system. Because it is now increased in size, they probably will remain bigger because one keeps at it with repetitive daily EECP treament (that is the trick in my view... repetitive daily treatments!... That is all what I can offer...
I compare that treatment to a "jump start" for our sick patients and compare that to benefits that some patients may have by exercising 30 minutes a day.
I know, I know, that does not prove anything... that is why I am personnally very interested in the multicentrer trial... on the other hand, I have high hopes that the benefits will be found (see previous literature).
That's all folks... Good luck
FHG |
