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The physiology thread

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The physiology thread

24 Mar 2013 19:38

It has come to my attention that threads frequently get diverted "off topic" by attempts to get into physiological discussions as to mechanisms, etc. to explain the phenomenon being discussed. Such diversions aren't always appreciated. Therefore, I think it reasonable to start a thread devoted to physiology, where any physiology topic cannot be considered off topic.

The last of these "off topic" discussions I was involved in had to do with VO2max and the physiological mechanisms that determine VO2max. There are three different camps here.

1. Noakes central governor theory (a neurological "black box" control mechanism)
2. The heart itself being the limiter.
3. Peripheral muscular effects causing the heart to look like it is the limiter (this is the theory I ascribe to)

Anyhow, any theory, to be correct, must explain all of the observed phenomenon. For instance, it must explain:

1. Why VO2max in the same person can vary, depending upon how it is measured (running, cycling, rowing (etc).
2. Why VO2max can vary depending upon hemoglobin levels or hydration status.
3. Why athletes in certain aerobic sports tend to have higher VO2max (on average) than athletes in other aerobic sports.
4. Why training (or stopping training) can change VO2max.

Anyhow, that is enough. I believe that it can all be pretty much explained by what is going on at the peripheral muscle level. Anyone who has a different viewpoint should feel free to present their arguments here and convince me I am wrong. But, of course, (unless your arguments are compelling) be prepared for me to try to convince you I am right.

Anyhow, in any of these other threads, if there is a need to go a littl off topic and discuss physiology, those discussions can be moved to this thread.
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FrankDay
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26 Mar 2013 02:38

Physiology is great topic for a thread. Can you explain what is peripheral muscular effects and how they make heart look like it is the limiter?

So what is the limiting factor? I believe that for road cycling it it is oxygen uptake and transport. Cycling is aerobic sport. The fact that almost all effective doping methods (epo, transfusions) target oxygen transport support this. This applies even for sprinters. You can't sprint if you have been in the red zone for most of the race.
perpetuum mobile
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29 Mar 2013 21:00

perpetuum mobile wrote:Physiology is great topic for a thread. Can you explain what is peripheral muscular effects and how they make heart look like it is the limiter?

So what is the limiting factor? I believe that for road cycling it it is oxygen uptake and transport. Cycling is aerobic sport. The fact that almost all effective doping methods (epo, transfusions) target oxygen transport support this. This applies even for sprinters. You can't sprint if you have been in the red zone for most of the race.
I will do my best. First, let's agree that VO2max is associated with maximum cardiac output. http://www.ncbi.nlm.nih.gov/pubmed/10647532 It is this simple relationship that causes people to say that VO2max is limited by the heart. But, is it really? Let's look at the factors that affect cardiac output.

Cardiac output is nothing more than stroke volume (the amount of blood ejected with each contraction) and heart rate (the number of contractions per minute). In physiology these will frequently be referred to as inotropy and chronotropy (affecting heart rate). There is one more issue that is involved in stroke volume that is sometimes included as part of inotropy and sometimes considered separately, which is the term venricular compliance, that is the the amount of blood that will enter the heart after each beat for any given filling pressure.

So, now we see that cardiac output depends on a lot of different things from HR, inotropy, compliance, and filling pressure. If we really want to understand what is limiting at VO2max we should be looking at these underlying components that, when added together, constitute "the heart" function. Is there anything that affects these?

Before we move on let's discuss muscle contraction and relaxation. One of the things that happen when we train is we are training the all of the mechanisms of the muscle involved in these activities. This involves making the high energy compounds necessary for contraction and relaxation. Mitochondrial density will increase as will many other microscopic and cellular changes occur. Of those that involve metabolic processes understand that these proteins and enzymes tend to work best in a very narrow range of pH and electrolytye concentrations. Any substantial change in any part of this cascade will result in a reduced ability.

So, now, when we get back to looking at what is going on at VO2max we need to try to explain why the cardiac output levels off and then drops as one goes past VO2max. To do this we should be looking at inotropy, chronotropy, compliance, and filling pressure. Filling pressure and HR doesn't change so we now need to look at inotropy (contractility), and compliance. It is clear they need to be changing, what could possibly be going on to cause those changes?

Well, remember, at VO2max we are well beyond threshold, meaning that at least some of the exercising muscles are anaerobic and those muscles will be utilizing, in part, anaerobic metabolism. Anaerobic metabolism involves the end product lactic acid, which is almost immediately buffered by the Bicarbonate system with the production of a CO2. It is this extra CO2 that causes us to breath much harder at this point to try to blow it off but the increase in CO2 production is so large (about 15 times the CO2 per ATP compared to aerobic metabolism). Anyhow, the end result of all this is, with time, the pH of the entire body (the bicarbonate system is highly water soluble so these changes occur throuout the entire body) system becomes more acidic and the enzymes necessary for optimal cardiac contraction and relaxation start to lose effectiveness. At this point we will start to see a reduction in cardiac output. But, the reasons for this drop comes from changes in both contractility and compliance stemming from lactic acid production occurring in the periphery.

Anyhow, there are a lot of things going on and this is a very simplistic explanation trying to get to all these interactions. But, from this, I think you can see why, even though on the surface it looks like the heart limits aerobic capacity, the changes that actually limit our aerobic capacity really start in the periphery.
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29 Mar 2013 22:37

How don't filling pressure and HR not change past VO2max?

As you said, cardiac output (CO) = heart rate (HR) x stroke volume (SV)

SV is determined by preload, afterload and contractility.

Preload (= venous return) is increased during exercise because of increased mean vascular filling pressure (because of increased vascular volume) and increased peripheral vascular resistance.

Afterload = peak load developed in the ventricular wall during systole. The amount of work performed by the heart is directly related to the amount of afterload, and afterload is largely proprotional to ventricular systolic pressure.

Contractility is an intrinsic property of cardiac muscle which allows cardiac muscle to change myocardial contractility and SV independent of preload and afterload. Contractility is primarily determined by sympathetic tone in the heart.

CO is increased 6-8 fold during strenuous exercise in an effort to increase transport of oxygen. Dilation of pulmonary vessels and decreased pulmonary vascular resistance are responsible for accommodating the additional pulmonary blood flow.

During exercise, the following occurs:
• demand for gas transport is not constant and depends on metabolism
• oxygen demands during exercise are met by increased blood flow, hemoglobin levels, and oxygen extraction from blood
• cardiac output increases which increases amount of blood flowing through lungs per minute to increase resulting in an increased uptake of oxygen in the lungs
• cardiac output is redistributed so that blood flow is increased to exercising muscles
• splenic contraction increases circulating erythrocytes, and hence hemoglobin, by 35%-50%
• however, increased PCV increases blood viscosity and decreases blood flow through capillaries and increases cardiac workload
• increased muscle blood flow and PCV increases oxygen delivery to muscle
• muscle also extracts greater amounts of oxygen from blood due to increased diffusion gradient for oxygen, as a result of decreased partial pressure of oxygen in muscle, and decreased affinity of hemoglobin for oxygen, due to high temperature of exercising muscle and release of CO2 and hydrogen ions
• myoglobin within muscle also provides a small store of oxygen, but the main function of myoglobin is transfer of oxygen with the muscle cell
• myoglobin is an iron-containing pigment but only has 1 heme group
• myoglobin dissociation curve is rectangular hyperbola due to 1 heme group
• oxygen affinity of myoglobin is high with 75% saturation at partial pressure of oxygen of only 20 mm Hg
• myoglobin only releases oxygen when intracellular partial pressure of oxygen is low

VO2 = gas properties x surface area x (PAO2 - PcapO2)/thickness of air-blood barrier; where gas properties = molecular weight and solubility of gas, in this case O2; surface area = alveolar surface area available for diffusion that is occupied by perfused pulmonary capillaries; PAO2 = alveolar O2 tension; PcapO2 = pulmonary capillary O2 tension; and thickness of air-blood barrier is non-disease states is < 1 um.

Oxyhemoglobin disassociation curve reflects the overall affinity of hemobglobin for O2 with left shifts of the curve = higher affinity for O2. Left shifts are caused by decreased PaCO2, decreased hydrogen ion concentration, decreased temperature, and decreased 2,3-diphosphoglycerate. Except for the last factor, all are increased during exercise, which decreases affinity of hemoglobin to O2.

These are just an example of some of the physiologic consequences to exercise where much more is at play than just CO. CO increases because of the need for O2 in exercising muscles and lungs, and this is ultimately determined by many complex pulmonary functions. However, what ultimately limits VO2max is the available alveolar surface area that is occupied by perfused pulmonary capillaries and alveolar O2 tension.
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30 Mar 2013 00:33

elapid wrote:How don't filling pressure and HR not change past VO2max?
I think it is a reasonable assumption that these numbers remain essentially constant over this small range at or around VO2max. Unless you have some data to suggest that HR drops at VO2max (accounting for the drop in CO) or that filling pressure drops while contractility remains constant I think this is a reasonable assumption. My experience dealing with failing hearts shows that both filling pressure and HR tend to increase while CO drops.

As you said, cardiac output (CO) = heart rate (HR) x stroke volume (SV)

SV is determined by preload, afterload and contractility.
Compliance also is involved in the SV equation

Preload (= venous return) is increased during exercise because of increased mean vascular filling pressure (because of increased vascular volume) and increased peripheral vascular resistance.
Preload is more technically a measure of muscle sarcomere stretch prior to contraction. It cannot be measured directly so indirect measurements such as filling pressure is used as a substitute. It has no direct relationship to venous return. I am interested in hearing how blood volume changes as we exercise. And, I think you will find that exercise is associated with a decrease in PVR.

Afterload = peak load developed in the ventricular wall during systole. The amount of work performed by the heart is directly related to the amount of afterload, and afterload is largely proprotional to ventricular systolic pressure.
The work performed by the heart is more directly related to cardiac output than afterload since the afterload doesn't increase that much during exercise (maximum about a doubling) while the CO can increase up to 5 times (5 to 25 l/min).

Contractility is an intrinsic property of cardiac muscle which allows cardiac muscle to change myocardial contractility and SV independent of preload and afterload. Contractility is primarily determined by sympathetic tone in the heart.
Contractility is an intrinsic property to cardiac muscle and it can be influenced by many things, including sympthetic stimulation, but it is independent of sympathitic tone since cardiac contractility is maintained in denervated hearts (transplanted hearts that have no sympathetic nerve endings) http://www.ncbi.nlm.nih.gov/pubmed/2017979 "This finding is consistent with a normal contractility of the transplanted, denervated human heart. Normal baseline contractility therefore is an intrinsic property of the intact heart, which is independent of autonomic neural control."

CO is increased 6-8 fold during strenuous exercise in an effort to increase transport of oxygen. Dilation of pulmonary vessels and decreased pulmonary vascular resistance are responsible for accommodating the additional pulmonary blood flow.
??? Most of what is going on in the pulmonary vessels during exercise is passive.

During exercise, the following occurs:
• demand for gas transport is not constant and depends on metabolism
• oxygen demands during exercise are met by increased blood flow, hemoglobin levels, and oxygen extraction from blood
oxygen demands during exercise are not met by increasing hemoglobin levels. Hemoglobin cannot change accutely except through bleeding or transfusion.
• cardiac output increases which increases amount of blood flowing through lungs per minute to increase resulting in an increased uptake of oxygen in the lungs
• cardiac output is redistributed so that blood flow is increased to exercising muscles
• splenic contraction increases circulating erythrocytes, and hence hemoglobin, by 35%-50%
The spleen, an organ about the size of your fist, holds enough blood that it can increase circulating hemoglobin 50%???
• however, increased PCV increases blood viscosity and decreases blood flow through capillaries and increases cardiac workload
??? While increasing PCV can increase viscosity it can also increase the amount of oxygen delivered per unit of blood and decrease cardiac work (it is why we give transfusions if HCT gets too low). Increasing HCT is only a problem if it is particularly high.
• increased muscle blood flow and PCV increases oxygen delivery to muscle
• muscle also extracts greater amounts of oxygen from blood due to increased diffusion gradient for oxygen, as a result of decreased partial pressure of oxygen in muscle, and decreased affinity of hemoglobin for oxygen, due to high temperature of exercising muscle and release of CO2 and hydrogen ions
???
• myoglobin within muscle also provides a small store of oxygen, but the main function of myoglobin is transfer of oxygen with the muscle cell
• myoglobin is an iron-containing pigment but only has 1 heme group
• myoglobin dissociation curve is rectangular hyperbola due to 1 heme group
• oxygen affinity of myoglobin is high with 75% saturation at partial pressure of oxygen of only 20 mm Hg
• myoglobin only releases oxygen when intracellular partial pressure of oxygen is low
What does the vast majority of the above have to do with the question being discussed: What is the limiter in VO2max

VO2 = gas properties x surface area x (PAO2 - PcapO2)/thickness of air-blood barrier; where gas properties = molecular weight and solubility of gas, in this case O2; surface area = alveolar surface area available for diffusion that is occupied by perfused pulmonary capillaries; PAO2 = alveolar O2 tension; PcapO2 = pulmonary capillary O2 tension; and thickness of air-blood barrier is non-disease states is < 1 um.
This relates to this conversation how?

Oxyhemoglobin disassociation curve reflects the overall affinity of hemobglobin for O2 with left shifts of the curve = higher affinity for O2. Left shifts are caused by decreased PaCO2, decreased hydrogen ion concentration, decreased temperature, and decreased 2,3-diphosphoglycerate. Except for the last factor, all are increased during exercise, which decreases affinity of hemoglobin to O2.
Again, your point as it relates to this topic?

These are just an example of some of the physiologic consequences to exercise where much more is at play than just CO. CO increases because of the need for O2 in exercising muscles and lungs, and this is ultimately determined by many complex pulmonary functions. However, what ultimately limits VO2max is the available alveolar surface area that is occupied by perfused pulmonary capillaries and alveolar O2 tension.
I would be happy to discuss any of these issues with you if you would like. Of course, physiology is complicated and almost everything affects everything else. It is why anesthesiologists, whose main job is to make sure that oxygen is delivered to the tissues under all circumstances, spend so much time trying to understand cardiopulmonary and oxygen delivery physiology, so they can recognize when something is going wrong and fix it, if possible, once recognized.

That having been said, the specific question under discussion though was what is the limiter at VO2max? If you have something to add that supports or goes against my basic premise I would be more than interested in hearing it.
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30 Mar 2013 04:39

What I would really like to know is how I ended up being such a mediocre cyclist whilst having a VO2 max of 82ml/kg.
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30 Mar 2013 05:00

simo1733 wrote:What I would really like to know is how I ended up being such a mediocre cyclist whilst having a VO2 max of 82ml/kg.
Your efficiency, technique, aerodynamics, (or something else) sucks?
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30 Mar 2013 12:10

FrankDay wrote:This relates to this conversation how?


Really? The equation for VO2 has no relation to the conversation on VO2max?

Very basically, VO2 = oxygen consumption and VO2max = maximal oxygen consumption. So everything you need to know about the limiters to VO2max are in the VO2 equation.

VO2 = gas properties x surface area x (PAO2 - PcapO2)/thickness of air-blood barrier.

Respiratory physiologists would know better than I, but I would assume that the properties of O2 and the thickness of the air-blood barrier would be constants. I am guessing the same for the alveolar surface area available for diffusion that is occupied by perfused pulmonary capillaries. So that leaves PAO2 and PcapO2 as the two main determinants and limiters of VO2 and hence VO2max.

PcapO2 increases during exercise because of dilation of the pulmonary vessels, including capillaries, as a result of invreased intravascular pressure from increased blood flow and decreased pulmonary vascular resistance because of release of factors such as nitric oxide.

Then look at PAO2: PAO2, alveolar oxygen tension, is the first step in the oxygen pathway and is important in all subsequent steps because PAO2 will always be greater than PaO2, or arterial oxygen tension. This oxygen pathway is essential because it represents the major function of the cardiorespiratory system (and hence VO2) which is to deliver oxygen to tissues and eliminate CO2 generated during tissue metabolism. The oxygen pathway is inspired O2 (PiO2) --> alveolar O2 (PAO2) --> arterial O2 (PaO2) --> O2 saturation (SpO2) --> O2 content (CaO2) --> O2 delivery. The conversion of PAO2 to PaO2 is dependent on pulmonary gas exchange. PaO2 determines SaO2 and this is represented in the oxyhemoglobin disassociation curve. CaO2, the amount of O2 carried by each 100ml of blood, is determined SpO2 and hemoglobin concentration. So dismissing any step in this pathway, such as the oxyhemoglobin disassociation curve, will limit your ability to interpret the limiters of VO2max.

Back to PAO2:
PAO2 = PiO2 - (PACO2/respiratory exchange ratio), therefore
PAO2 = (barometric pressure - partial pressure of water vapor) x FiO2 - (PACO2/respiratory exchange ratio); where barometric pressure is 760mm Hg at sea level, partial pressure of water vapor is 47mm Hg at saturation and normal body temperature, FiO2 is 0.21 at room temperature, and the respiratory exchange ratio is a constant at 0.83.

Hence, PAO2 = (760 - 47) x 0.21 - (PACO2/0.83); which means PAO2 is determined by PACO2.

PACO2 is determined by the rate of CO2 production (VCO2) in relation to the amount of alveolar ventilation by the following equation: (barometric pressure - partial pressure of water vapor) x VCO2/alveolar ventilation.

So, essentially, PAO2 decreases when PACO2 increases.

Strenuous exercise results in minimal O2 content of venous blood returning to lungs (ie, increased PACO2 and decreased PAO2), increased cardiac output and velocity through pulmonary capillaries (ie, increased PcapO2), and shorter time for diffusion of O2 (decreased exchange).

So when you look back at the VO2 formula, the two non constants are PAO2, which decreases with strenuous exercise for the aforementioned reasons, and PcapO2, which increases with exercise. While cardiac output is involved in O2 delivery, it is actually the respiratory system which is the limiter to VO2max.
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30 Mar 2013 12:33

Frank, as a surgeon, I need to have a good knowledge of cardiorespiratory physiology. You seem to have a very myopic view of this topic and perhaps accepting the importance of the respiratory component of determining VO2max rather than concentrating on the cardiac component may assist in your understanding of the limiters of VO2max.

To answer some of your statements/questions about cardiorespiratory physiology:
- filling pressure decreases with increased HR because the more rapid the HR the less time the ventricles have to fill which decreases filling pressure
- preload is determined by venous return because venous return determines atrial pressure and atrial pressure determines the amount of stretch on the ventricle prior to contraction; venous return is increased during exercise because of increased blood volume from spelnic contraction and increased peripheral vascular resistance
- amount of work performed by the heart is directly related to afterload; argue all you like, but the cardiorespiratory physiologists who have written all the seminal textbooks from which we all study for our board exams state that amount of work performed by the heart is directly related to afterload
- cardiac contractility is determined by sympathetic tone; because contractility is maintained in a denervated heart does not mean that sympathetic tone does not play a role in contractility in an exercise state; exercise increases sympathetic tone and hence increases contractility
- hemoglobin levels increase during exercise because of increased circulating red blood cell levels secondary to splenic contraction; more red blood cells, more hemoglobin mass, more O2 carrying capability
- yes, the spleen contraction can increase circulating red blood cells by 35-50%
- increased blood viscosity increases cardiac workload because more work is required to perfuse capillaries; your statement is true for disease states such as the various causes of polycythemia, but at a physiologic level small changes in blood viscosity can have important effects when you are already on the rivet
- your question marks and queries regarding CO2 production during exercise and the oxyhemoglobin disassociation curve: see above for the importance of CO2 in determining VO2 (and hence VO2max); and for the importance of the oxyhemoglobin disassociation curve in determining O2 saturation and subsequently O2 content.
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30 Mar 2013 17:30

elapid wrote:Frank, as a surgeon, I need to have a good knowledge of cardiorespiratory physiology. You seem to have a very myopic view of this topic and perhaps accepting the importance of the respiratory component of determining VO2max rather than concentrating on the cardiac component may assist in your understanding of the limiters of VO2max.
I really don't want to get into a back and forth as to training or understanding is better as the important thing should be what is said, not who says it. However, some do try to make that argument as I have been told by some here trained as exercise physiologists that I couldn't possibly have the same understanding of this stuff that they do because my patients are not exercising. That having been said, I think you will agree that the average anesthesiologist has a better understanding of cardioulmonary physiology than the average surgeon. And, I suspect you would also agree that being an exercise physiologist is not evidence that one's understanding of physiology is superior to anyone else.

To answer some of your statements/questions about cardiorespiratory physiology:
- filling pressure decreases with increased HR because the more rapid the HR the less time the ventricles have to fill which decreases filling pressure
Perhaps you should define filling pressure here. Filling pressure as normally measured doesn't change with HR at all since it is normally measured proximal to the heart. End-diastolic pressure might drop a bit from this issue but this is not the same as filling pressure.
- preload is determined by venous return because venous return determines atrial pressure and atrial pressure determines the amount of stretch on the ventricle prior to contraction; venous return is increased during exercise because of increased blood volume from spelnic contraction and increased peripheral vascular resistance
preload is determined by lots of things, venous return being just one.
- amount of work performed by the heart is directly related to afterload; argue all you like, but the cardiorespiratory physiologists who have written all the seminal textbooks from which we all study for our board exams state that amount of work performed by the heart is directly related to afterload
Well, that is one factor if one is using the term correctly. Afterload is not the same as the measured pressure in the ventricles, it is the wall stress seen. So, a dilated heart with a peak pressure of say 180mmhg can actually have a higher afterload than a normal sized heart with a peak pressure of 200mmhg. Or, a heart in failure because of a large left-right shunt? In that instance is it better to reduce afterload or reduce the shunt in trying to reduce the work requirements of the heart? Anyhow, if you are reading these experts as saying that the work performed by the heart is directly related to afterload (and nothing else) then I would submit you are misreading their writings. How about a link to support that statement?
- cardiac contractility is determined by sympathetic tone; because contractility is maintained in a denervated heart does not mean that sympathetic tone does not play a role in contractility in an exercise state; exercise increases sympathetic tone and hence increases contractility
Of course the sympathetic nervous system can play a role in changing cardiac contractility. It is simply not the only influence on this and, even if it were, is not associated with what is going on at VO2max (unless, of course, you can provide a link that says otherwise).
- hemoglobin levels increase during exercise because of increased circulating red blood cell levels secondary to splenic contraction; more red blood cells, more hemoglobin mass, more O2 carrying capability
Exactly how large is this effect? Do you have a link? How is it that athletes that have had splenectomies don't seem to see this as an adverse event in their career development.
- yes, the spleen contraction can increase circulating red blood cells by 35-50%
link to support this please
- increased blood viscosity increases cardiac workload because more work is required to perfuse capillaries; your statement is true for disease states such as the various causes of polycythemia, but at a physiologic level small changes in blood viscosity can have important effects when you are already on the rivet
link please to support this statement. By your reasoning EPO should have adverse affects on the athlete because of the increased viscosity associated with the increase in RBC mass.
- your question marks and queries regarding CO2 production during exercise and the oxyhemoglobin disassociation curve: see above for the importance of CO2 in determining VO2 (and hence VO2max); and for the importance of the oxyhemoglobin disassociation curve in determining O2 saturation and subsequently O2 content.
??? huh? What does any of this have to do with determining VO2max limit?

I was thinking about a couple of clinical situations that affect cardiopulmonary physiology somewhat similar to what happens at VO2max (except the VO2max effects are transient and reversible). What is going on to cardiopulmonary physiology during gram negative sepsis or a metabolic acidosis? In these instances it isn't the heart itself that is causing the cardiac problems but the milieu it finds itself in. By the same token, it doesn't seem that the heart "failures" seen at VO2max are due to problems in the heart itself by rather because the milieu it finds itself in is changing.
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30 Mar 2013 21:53

OK. I give up, Frank. This thread is yours and yours alone. I'm not coming back. Your myopic concentration on cardiac function and disregard of the respiratory system is the reason why you do not understand the limiters of VO2max. Goods luck with having a conversation with yourself. Bye.
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30 Mar 2013 22:24

elapid wrote:OK. I give up, Frank. This thread is yours and yours alone. I'm not coming back. Your myopic concentration on cardiac function and disregard of the respiratory system is the reason why you do not understand the limiters of VO2max. Goods luck with having a conversation with yourself. Bye.
I am sorry you feel that way but I got the feeling we were debating apples and oranges. One of the things that happens at VO2max is cardiac output levels then drops. Perhaps that is why I am focused on that aspect of VO2max since any explanation of that limit must be able to explain that behavior. I never did understand why you were bring up all this other stuff that I considered extraneous to this problem, especially when your points were never presented with links to any supporting scientific studies.

Oh well, maybe Dr. Coggan will show up.
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04 Apr 2013 06:28

I would like to resuscitate this thread, because it seems to me it’s very relevant background to a recent discussion I have been part of in the Clinic. Race Radio claims that the great success of Armstrong and Ullrich as GT riders resulted from an ability to get more improvement from blood doping—EPO in the 90s, transfusions combined with some EPO in the past decade—than their rivals. More specifically, the claim is that LA and Ulle had more muscle mass—part of it was a natural advantage, and it was augmented by steroids and other PEDs—and that this muscle was needed to make “full use” of the additional RBCs acquired from blood doping.

As far as I can tell from searching, there are no scientific studies to back up this claim, though RR does provide a quote from JV, referring to a Finnish study that JV himself admits he can no longer find. So evaluation of this idea has to be theoretical rather than empirical. This is where this thread comes in, I hope.

According to the abstract linked by the OP in this thread, oxygen delivery, rather than oxygen extraction at the muscle, is the limiting factor for V02 max. One important line of evidence supporting this is that V02 is increased by blood doping. Since oxygen extraction is not limiting, anything that increases the amount of oxygen taken up by the blood, and subsequently delivered to the tissues, will increase oxygen usage. It seems that there is probably no realistic limit. Any amount of oxygen you can get into your blood will be used by the muscles, at whatever efficiency they happen to operate at.

The notion proposed by RR, it seems to me, would provide an interesting test of this view. What would happen if subjects, following a baseline measurement of V02, went on a sustained muscle building program? Would their V02 increase? According to that abstract, and most other views of V02, no. Since oxygen extraction is not limiting, if one increases the muscle mass there will be no increase in oxygen intake or in overall extraction.

AFAIK, no study of this kind has ever been carried out. But if V02 did increase under these circumstances, it would provide not only some support for RR’s claim, but simultaneously evidence against the view that V02 is primarily determined by CO. It would suggest that peripheral factors do indeed regulate V02, though I’m not sure the results could be explained in terms of lactic acid and lowered pH.

However, if V02 did not change, and the CO view was not threatened, this would not necessarily count as evidence against RR’s claim. We know that during intense exercise, more oxygen is shunted to the skeletal muscles. If one adds muscle mass via a program of PEDs, it’s reasonable to suppose that this shunting might become more pronounced. So in this limited sense, the notion that adding muscle mass allows an athlete to take better advantage of blood boosting is probably correct. But stated in this way, the claim is much weaker. If one adds more muscle mass, presumably more oxygen will be distributed to the muscles regardless of whether one is operating with a normal or an artificially elevated hematocrit. It’s like saying large leg muscles help a sprinter go faster. Of course.

Frank, if you’re reading this, you might also want to check out the discussion in the Clinic; it’s in the Jan Ullrich thread. I told Andy Coggan about it, and he commented briefly, but not on the actual theory that RR is claiming.
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04 Apr 2013 16:12

Merckx index wrote:I would like to resuscitate this thread, because it seems to me it’s very relevant background to a recent discussion I have been part of in the Clinic. Race Radio claims that the great success of Armstrong and Ullrich as GT riders resulted from an ability to get more improvement from blood doping—EPO in the 90s, transfusions combined with some EPO in the past decade—than their rivals. More specifically, the claim is that LA and Ulle had more muscle mass—part of it was a natural advantage, and it was augmented by steroids and other PEDs—and that this muscle was needed to make “full use” of the additional RBCs acquired from blood doping.
This seems like a very simplistic view of things made by people who really don't understand how oxygen gets from the lungs to where it is really needed, the mitochondria. See below.

As far as I can tell from searching, there are no scientific studies to back up this claim, though RR does provide a quote from JV, referring to a Finnish study that JV himself admits he can no longer find. So evaluation of this idea has to be theoretical rather than empirical. This is where this thread comes in, I hope.
I am not sure how such a study would be designed. The difficulty with any study is not in the data gathering but in the interpretation of the data anyhow.

According to the abstract linked by the OP in this thread, oxygen delivery, rather than oxygen extraction at the muscle, is the limiting factor for V02 max. One important line of evidence supporting this is that V02 is increased by blood doping. Since oxygen extraction is not limiting, anything that increases the amount of oxygen taken up by the blood, and subsequently delivered to the tissues, will increase oxygen usage. It seems that there is probably no realistic limit. Any amount of oxygen you can get into your blood will be used by the muscles, at whatever efficiency they happen to operate at.
This seems sort of silly since VO2max is, by definition, the amount of oxygen extracted. Of course, oxygen delivery and oxygen extraction are related. So, the question becomes, what really is the limiter. What physiological component in the oxygen delivery cascade prohibits further increase. In other words, what is the weakest link in the chain? One cannot answer that unless one understands all of the links in the chain so one can analyze which might be the weakest link.

The notion proposed by RR, it seems to me, would provide an interesting test of this view. What would happen if subjects, following a baseline measurement of V02, went on a sustained muscle building program? Would their V02 increase? According to that abstract, and most other views of V02, no. Since oxygen extraction is not limiting, if one increases the muscle mass there will be no increase in oxygen intake or in overall extraction.
Muscle mass is only part of the equation because if you went to the local power lifting studio, where there is a lot of muscle mass, and measured VO2max you would find it to be quite low. While muscle mass is important, the most important aspect of the muscle allowing for oxygen delivery is capillary density. This is increased by training.

AFAIK, no study of this kind has ever been carried out. But if V02 did increase under these circumstances, it would provide not only some support for RR’s claim, but simultaneously evidence against the view that V02 is primarily determined by CO. It would suggest that peripheral factors do indeed regulate V02, though I’m not sure the results could be explained in terms of lactic acid and lowered pH.
I guess it would give some support but, as I said before, the difficult part of any study is the interpretation of the data. Such a result could support many hypotheses, including, IMHO, the correct one.

However, if V02 did not change, and the CO view was not threatened, this would not necessarily count as evidence against RR’s claim. We know that during intense exercise, more oxygen is shunted to the skeletal muscles. If one adds muscle mass via a program of PEDs, it’s reasonable to suppose that this shunting might become more pronounced. So in this limited sense, the notion that adding muscle mass allows an athlete to take better advantage of blood boosting is probably correct. But stated in this way, the claim is much weaker. If one adds more muscle mass, presumably more oxygen will be distributed to the muscles regardless of whether one is operating with a normal or an artificially elevated hematocrit. It’s like saying large leg muscles help a sprinter go faster. Of course.
Shunting to increased muscle mass won't be increased unless one also does the extra work to increase or maintain the capillary density of the new muscle. You can't increase oxygen utilization unless you can increase oxygen delivery to the mitochondria. see below.

Frank, if you’re reading this, you might also want to check out the discussion in the Clinic; it’s in the Jan Ullrich thread. I told Andy Coggan about it, and he commented briefly, but not on the actual theory that RR is claiming.
I will take a look at this but I can almost assure you what they are saying is complete BS.

So, here is what is going on regarding oxygen delivery. Except for the pumping of blood from the lungs to the muscles, it is almost entirely passive and due to diffusion. Diffusion works under known laws. The rate of transfer depends upon the diffusion gradient and the distance (and, possibly, temperature may play a role if muscle temperature changes). What is the diffusion gradient of oxygen from the capillary to the mitochondria? Well, it is about 90-98 under normal circumstances with a oxygen concentration of about 95mmhg in the arterial end of the capillary and about 1mmhg at the mitochondria. The body does what it can to maintain an oxygen concentration of 1 mmhg at the mitochondria. When we are at rest most of the pre-capillary sphincters are closed, increasing the diffusion distance and keeping oxygen concentration at the capillary where it likes to be. As we exercise, additional capillaries open up, increasing blood flow but, more importantly, decreasing mean diffusion distance, increasing oxygen delivery. Pushing more blood through the same few capillaries would not increase oxygen delivery to any extent. As we exercise more, oxygen levels at the end capillary fall, decreasing the oxygen gradiant. Eventually, the ability to deliver oxygen via this diffusion mechanism is overwhelmed and the muscles go anaerobic. These limits only occur in the skeletal muscle and not in the heart, under normal conditions. The key to increasing oxygen delivery is training that increases capillary density and lowers the mean distance between capillary and mitochondria in the skeletal muscle.

At very high oxygen demand no further capillaries can be utilized so oxygen concentration at the capillary will start to drop and the athlete starts to go anaerobic at the most distant mitochondria. All a drug like EPO does is delay this drop. Anyone who tries to suggest that somehow Armstrong or Ullrich were dominant because they were, somehow, more sensitive to these drugs than the average doper, ignores the possibility that they might have both trained harder (or smarter) than their competition and used those drugs also.

In my opinion, all evidence points to the fact that the absolute limiter to the delivery of oxygen during exercise in any individual is the mean diffusion distance between capillary and mitochondria in the muscles being used.
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04 Apr 2013 16:31

Merckx index wrote:Frank, if you’re reading this, you might also want to check out the discussion in the Clinic; it’s in the Jan Ullrich thread. I told Andy Coggan about it, and he commented briefly, but not on the actual theory that RR is claiming.
The overall effects of EPO would be related to the amount of exercised muscle mass. But, everyone benefits and it is all relative. There simply is no evidence that drugs like EPO do or might affect different riders differently. To make a claim that this explains Armstrong's or Ulrich's dominance is simply pulling hypotheses out of thin air.

Edit: There is one other thing that interferes with such a simplistic interpretation and that is the energy cost of maintaining body elements. To make muscle mass requires substantial energy cost just as it does to make new capillaries. If one doesn't utilize these elements then they will atrophy. That is why it is so difficult to have lots of muscle mass and lots of aerobic capacity, we only have so much time to train these two completely different elements. That is why strength athletes have large muscles but no aerobic capacity, they only train one aspect. And, it is why marathon runners have small muscles and lots of capillaries, they have no need for a lot of muscle strength. Your body composition is dictated by how you train but everything you do has a maintenance cost. If you don't keep using it then the body will let it atrophy, just ask any astronaut after several months in space what has happened to their abilities.
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04 Apr 2013 17:24

FrankDay wrote:The overall effects of EPO would be related to the amount of exercised muscle mass. But, everyone benefits and it is all relative. There simply is no evidence that drugs like EPO do or might affect different riders differently. To make a claim that this explains Armstrong's or Ulrich's dominance is simply pulling hypotheses out of thin air.


To the bolded, I would agree if you limit your claim to the idea there's no research in this area. An enormous volume of research shows response varies in a population given a drug. Pick any number of double-blind legitimate drug trials and you'll discover that humans respond differently to the same drug, same dose. Why would EPO be different?
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04 Apr 2013 18:15

DirtyWorks wrote:To the bolded, I would agree if you limit your claim to the idea there's no research in this area. An enormous volume of research shows response varies in a population given a drug. Pick any number of double-blind legitimate drug trials and you'll discover that humans respond differently to the same drug, same dose. Why would EPO be different?
Well, the dose response to epo may vary, as would be expected, but the response to changing hct should be exactly the same. "None" of these guys got caught (even in the age of the blood passport) so we can expect that they all pretty much had the same dose response curve and use a similar "evasive" protocol. EPO is about increasing the ability to deliver oxygen to the tissues by increasing the RBC mass/concentration. Except in certain disease states, we would expect all athletes to respond the same to changing concentrations of RBC's. It is simply crazy that people are trying to explain Armstrong's improved gross efficiency over the years, as measured by Coyle, at the feet of epo use (or any other PED).
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04 Apr 2013 22:10

FrankDay wrote:It is simply crazy that people are trying to explain Armstrong's improved gross efficiency over the years, as measured by Coyle, at the feet of epo use (or any other PED).


Another strawman.

Coyle himself said that the drug use facilitated the high volume of training that Armstrong performed. The years of riding the bike led to the improved efficiency seen (disputes over measurement, ergs, self reported weight aside).
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05 Apr 2013 16:21

my simplistic view...

Seems that a large amount of 'good training' increases capillary and mitochondria growth, and that EPO is beneficial because it increases the amount of O2 in the blood that is available for up-take by the muscles. EPO is probably also useful because it helps make the large amount of training possible by delaying fatigue, and reducing recovery time.

Jay Kosta
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05 Apr 2013 17:44

JayKosta wrote:my simplistic view...

Seems that a large amount of 'good training' increases capillary and mitochondria growth, and that EPO is beneficial because it increases the amount of O2 in the blood that is available for up-take by the muscles. EPO is probably also useful because it helps make the large amount of training possible by delaying fatigue, and reducing recovery time.

Jay Kosta
Endwell NY USA

EPO does increase the amount of oxygen carried in the blood even though it doesn't increase the partial pressure of oxygen in the blood. So, the drop off in partial pressure for any given metabolic effort will be less and the the anerobic threshold will be delayed.

Now, if EPO were being used all the time it might actually reduce the capillary density in the muscles because the body would sense it is getting enough oxygen so the stimulus for making new capillaries would be reduced (unless, of course, they increased the amount of work done in training and kept the level constant year rouund). It seems to me that the major benefit of EPO would come from its race day benefits, not as a training aid.

I have no data that supports or rejects whether EPO has any effect on fatigue.
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