1962 Circulation Handbook--Was Dr. Guyton correct?

[rsweeney]

All right y'all, it's pretty amazing where my cardiovascular physiology journey has taken me. One question leads to an answer and then that answer leads to another question Well, I have come to the end of the road, and it's quite a paradox. Where Dr. Guyton's contributions have been a big help in my search for the answer his ideas have now confused me---maybe I, for the last time, turn to the great and brilliant minds of SDN. Following is an article from the 1962 Handbook of Physiology ~Circulation~ by Dr. Guyton when he first introduced the "Guyton analysis" or what we students commonly know as the cardiac and systemic function curves. My focus, however, is on Guyton's analysis of the relationship between increased vasomotor tone and its effect on the vascular function curve.

THE PASSAGE:
"Increased vasomotor tone has been caused by infusion of a sympathomimetic drug [epinephrine]. [As the rate of the sympathomimetic drug infusion was increased, the vascular function curve shifts in a parallel fashion up and to the right exactly like it does in a blood transfusion]....The slope of the venous return curve did not change, which is why it shifted in a parallel fashion. On second thought, one can understand why this is true. When vasomotor tone [arteriolar tone] is increased throughout the circulation while blood volume remains constant, pressures everywhere in the circulation will tend to rise because of tightening of the vessels around the blood. But, if any single segment of the circulation constricts, some other segment of the circulation must dilate. On average, then, for every constriction that occurs in the systemic circulation following the injection of epinephrine, there had to be equal dilation everywhere else. Indeed, measurements have shown that, as the arterioles constrict under these conditions, there is a tendency for the veins to dilate even though the walls of the veins to tighten to a very great extent. This elevates mean systemic pressure but does not increase the resistance to blood flow from the systemic veins toward the heart. In essence, then, we can say that an increase in vasomotor tone effect venous return principally by increasing the mean systemic pressure, and, usually, an increase in vasomotor tone does not increase the average resistance that opposes the return of blood to the heart."


Issue 1)
So do y'all see the problem. To this date ALL texts and board review series books say that an increase in vasomotor tone [which is the same thing as increased TPR] will NOT change the mean systemic pressure because the compliance and volume changes of the arterioles contribute insignificantly to the mean systemic pressure. For this reason, all texts have increased TPR shifting the vascular and cardiac function curve downward, with NO change in mean systemic pressure!

Issue 2)
"But, if any single segment of the circulation constricts, some other segment of the circulation must dilate. On average, then, for every constriction that occurs in the systemic circulation following the injection of epinephrine, there had to be equal dilation everywhere else...Indeed, measurements have shown that, as the arterioles constrict under these conditions, there is a tendency for the veins to dilate even though the walls of the veins tighten to a very great extent."

----What does that mean? All I know is that if the arterioles constrict, then TPR is up---period. The veins dilate at the same time--what? If that was the case, then vascular function curves as we learn them are full of it. The bottom line is this. If the veins do indeed dilate as the arterioles constrict, the vascular function curve would be WAY different than what is presented to us in text books AND in the classroom. Here is a description of what the vascular function curve should look like in Guyton's scenerio, where the arterioles constrict while the veins simultaneously dilate--in my point of view:

The vascular function curve will move downward in a parallel fashion as a result of venous dilation [or increased venous compliance]. Thus, a lower mean systemic pressure will be reached. The vascular function curve will then rotate in a counter-clockwise fashion about this new mean systemic pressure as a result of the increased TPR. That is how it should look.

Issue 3
So what/why is Guyton talking about folks, when he says:

1)Arteriolar constriction causes a parallel shift upward [like in a transfusion]
2)The veins simultaneously dilate when a segment of the arterioles constrict
3)What does he mean when he says "if any single segment of the circulation constricts". What is "a segment"?
4)increased vasomotor tone [increased TPR] causes a parallel shift upward on the vascular function curve----YEAH THIS IS TOTALLY WRONG

All I know is that only two things cause a parallel shift upward on the vascular function curve and they are as follows--according to recent texts:

1)Increased venous tone [decreased venous compliance]
2)Rapid transfusion of blood

Does it have something to do with the sympathomimetic drug? Or, has Guyton been correct all these years and current physiology professors/authors have simply been misinterpreting him, thus presenting us with false information in books and in the classroom?

Come on experts, this is the last big challenge!

What do you think?

Wow, this is a long one


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[wy2th]

Trust me, rsweeney has always been like this. He finally got me to register on SDN to type my response in. I gave him a verbal response, but I will type it in to see if SDN agrees. It's a clever find-I must admit. Since it was 1962 and Guyton was just coming up with this idea, a lot of ideas he had then were just that. His ideas then were not as refined as they are now.

Issue 1)
So do y'all see the problem. To this date ALL texts and board review series books say that an increase in vasomotor tone [which is the same thing as increased TPR] will NOT change the mean systemic pressure because the compliance and volume changes of the arterioles contribute insignificantly to the mean systemic pressure. For this reason, all texts have increased TPR shifting the vascular and cardiac function curve downward, with NO change in mean systemic pressure!

I would follow what current books say. The word vasomotor refers to the arteroles. So, if the arterioles constrict, then TRP will go up as you said. Also, as you said, MSFP will not change "because the compliance and volume changes of the arterioles contribute insignificantly to the mean systemic pressure".

Issue 2)
"But, if any single segment of the circulation constricts, some other segment of the circulation must dilate. On average, then, for every constriction that occurs in the systemic circulation following the injection of epinephrine, there had to be equal dilation everywhere else...Indeed, measurements have shown that, as the arterioles constrict under these conditions, there is a tendency for the veins to dilate even though the walls of the veins tighten to a very great extent."
----What does that mean? All I know is that if the arterioles constrict, then TPR is up---period. The veins dilate at the same time--what? If that was the case, then vascular function curves as we learn them are full of it. The bottom line is this. If the veins do indeed dilate as the arterioles constrict, the vascular function curve would be WAY different than what is presented to us in text books AND in the classroom. Here is a description of what the vascular function curve should look like in Guyton's scenerio, where the arterioles constrict while the veins simultaneously dilate--in my point of view:

The vascular function curve will move downward in a parallel fashion as a result of venous dilation [or increased venous compliance]. Thus, a lower mean systemic pressure will be reached. The vascular function curve will then rotate in a counter-clockwise fashion about this new mean systemic pressure as a result of the increased TPR. That is how it should look.

I am not too sure what that meant when he said "if any single segment of the circulation constricts, some other segment of the circulation must dilate." Unless the drug is having some counter-effect on the veins causing them to dilate, then I don't know how else to explain it. It takes a lot for those veins to dilate. Since, however, he specifically points out that the arterioles are constricting then as we know today TPR will go up and the MSFP will not change. He was wrong. Your "point of view" of how the vascular function curve will look is right on. Actually, in exercise, the vascular function curve moves to the right in a parallel fashion due to the sympathetic venous constriction AND THEN the vascular function curve will shift in a counter-clockwise fachion about that new MSFP due to the increased TPR.


Issue 3
So what/why is Guyton talking about folks, when he says:

1)Arteriolar constriction causes a parallel shift upward [like in a transfusion]

-This is incorrect

2)The veins simultaneously dilate when a segment of the arterioles constrict

-It might have something to do with the drug---anybody else wanna take a shot at this?

3)What does he mean when he says "if any single segment of the circulation constricts". What is "a segment"?

-I think what he meant was that instead of the entire collection of arteries and arterioles constriction, only a select few do---maybe.

4)increased vasomotor tone [increased TPR] causes a parallel shift upward on the vascular function curve----YEAH THIS IS TOTALLY WRONG

-I agree with you. It should be increased venomotor tone causes a parallel shift upward on the vascular function curve. But increased vasomotor tone WILL cause increased TPR--which will move the vascular function curve in a counter-clockwise fashion about that unchanged MSFP.

All I know is that only two things cause a parallel shift upward on the vascular function curve and they are as follows--according to recent texts:

1)Increased venous tone [decreased venous compliance]
-That is correct
2)Rapid transfusion of blood
-That is correct

Does it have something to do with the sympathomimetic drug? Or, has Guyton been correct all these years and current physiology professors/authors have simply been misinterpreting him, thus presenting us with false information in books and in the classroom?
It was not well understood yet is probably the best answer.

My 2 cents

WY

 

[orthoman5000]

Nooooooooo.......Cardiovascular physiology........must run away

 

[omarsaleh66]

yo i read guyton's stuff. it all makes senes.

issue 1: i have to see what u dont understand in the recent textbooks to answer this.


issue 2: in sympathetic, u constrict the arteries, and not the veins so the vascular function curve reacts the same way as a transfusion, an increase in blood to the heart.

issue 3:


1)Arteriolar constriction causes a parallel shift upward [like in a transfusion]


yes

2)The veins simultaneously dilate when a segment of the arterioles constrict

yes

3)What does he mean when he says "if any single segment of the circulation constricts". What is "a segment"?

segment = arteries, other segment is veins


4)increased vasomotor tone [increased TPR] causes a parallel shift upward on the vascular function curve----YEAH THIS IS TOTALLY WRONG


i see what guyton is saying, in case of sympathetics, yes, it will constrict arteries, more blood will go to veins, they will dilate due to compliance, and there will be a increase in venous return.


Does it have something to do with the sympathomimetic drug?

yes!! big time


Or, has Guyton been correct all these years and current physiology professors/authors have simply been misinterpreting him, thus presenting us with false information in books and in the classroom?


i think guyton's article is old but is correct.The BRS review book isnt that clear, its kinda hard to analyze the guyton article with the use of BRS in my opinion


later and gluck

Omar

 

[CYP2E1]

Hi Richard

I am not going to pretend that I completely understand your questions, so if my answers fail you please forgive me. AC Guyton (May he rest in peace) is correct I believe, perhaps not well worded but correct. I think his choice of words can be misleading.

Q1. Firstly with regard to:
?To this date ALL texts and board review series books say that an increase in vasomotor tone [which is the same thing as increased TPR] will NOT change the mean systemic pressure because the compliance and volume changes of the arterioles contribute insignificantly to the mean systemic pressure. For this reason, all texts have increased TPR shifting the vascular and cardiac function curve downward, with NO change in mean systemic pressure?

A1. This is not how I read my textbooks, eg B&L pp207 ?? if blood volume remains constant, only changes in venous tone can alter the mean circulatory pressure appreciably. Hence mean circulatory pressure rises with increase venomotor tone and falls with diminished tone?.

This is quite different from the negligible effect changes arteriolar tone (which contain only 3-5% of total blood volume) have on mean circulatory pressure.

So Guyton is correct that ?[As the rate of the sympathomimetic drug infusion was increased, the vascular function curve shifts in a parallel fashion up and to the right exactly like it does in a blood transfusion]....? and that ?In essence, then, we can say that an increase in vasomotor tone effect venous return principally by increasing the mean systemic pressure, and, usually, an increase in vasomotor tone does not increase the average resistance that opposes the return of blood to the heart?

Also increased TPR and increased vasomotor tone are not the same thing. Whilst in most cases increased vasomotor tone will increase arteriolar resistance (in most vascular beds) and therefore lead to an increase in TPR it is a causal relationship not an equivalence.

Q2 Secondly ?Indeed, measurements have shown that, as the arterioles constrict under these conditions, there is a tendency for the veins to dilate even though the walls of the veins tighten to a very great extent." ???!!!!

I need more info I am thinking that he could be referring to pressure as decreased volume with decrease lumen radius or the effect of sympathomimetic drugs on beta adrenoreceptors causing dilation (but then why tightened veins??)

Q3 Thirdly with regard to ?So what/why is Guyton talking
1) Arteriolar constriction causes a parallel shift upward [like in a transfusion]

A3a. No increase venomotor tone causes a parallel shift as in transfusion; increase arteriolar vasoconstriction causes a clockwise rotation in the vascular function curves (VFC) B&L pp207.

4) Increased vasomotor tone [increased TPR] causes a parallel shift upward on the vascular function curve----YEAH THIS IS TOTALLY WRONG

A3d. Look at a plot of CVP(y axis) and CO (y axis) and you will see the parallel shift as per transfusion if venomotor tone is increased. Just look at graphs on pp206 in B&L. You are correct that increase TPR however will give you the shift as in A3a. In my view is it possible that there has been a failure to differentiate between arteriolar tone, venomotor tone and mean circulatory pressure.

 

[rsweeney]

"an increase in vasomotor tone does not increase the average resistance that opposes the return of blood to the heart"

CYP, increased vasomotor tone should increase the average resistance--right? I thought epinephrine will constrict ALL vessels, thus causing vasomotor tone to increase everywhere. So, this "EVERYWHERE" must include the veins AND arterioles , right? So, if the arterioles are constricting then TPR should go up. However, at the same time the veins are constricting so venous return goes up. So, with epinephrine injected intravenously, the increased venous tone will shift the vascular funtion curve in a parallel fashion to a new mean systemic pressure. But, since the arterioles are constricting as well, the vascular function curve should shift in a counterclockwise fashion about the new mean system filling pressure.

Q2 Secondly ?Indeed, measurements have shown that, as the arterioles constrict under these conditions, there is a tendency for the veins to dilate even though the walls of the veins tighten to a very great extent." ???!!!!

I need more info I am thinking that he could be referring to pressure as decreased volume with decrease lumen radius or the effect of sympathomimetic drugs on beta adrenoreceptors causing dilation (but then why tightened veins??)

In a related article, Guyton states, "Since blood is incompressible, if all the vessels are attempting to constrict simultaneously nothing will happen except raise the mean systemic pressure. But, as one vessel constricts under these conditions there has to be equal dilation somewhere else. Thus, mean systmeic pressure increases and the resistance to venous return is unchanged."

My guess is that the epinephrine is attempting to constrict everything at the same time. But, since the arterioles have way more muscle mass than the veins they "win" the constriction battle per se. So, as the arterioles constrict as a result of the epinephrine, the veins dilate because of the extra volume being sent over to them from the constricting arterioles. However, the tone [tightening] still increases in the veins because the muscles are still constricting around the veins from the epinephrine. Thus, as the venomotor tone increases venous return increases.

The only error in "the equal dilation for every constriction" theory is that it presumes TPR will NEVER increase or decrease. This is because whenever one vessel constricts the volume will HAVE be translocated somewhere else causing another vessel to dilate. Thus, when you see vascular function curves in which there is an increase or decrease in TPR [without a change in mean systemic pressure], you have to assume that the veins are perhaps not being targeted by sympathetic impulses--I guess. Because, if the veins were being targeted by sympathetic impulses the tone in them would go up and mean systemic pressure would change. If Guyton is correct, then any time the arterioles constrict to increase TPR, then the veins will equally dilate thus resulting in a zero net radius change---thus TPR will ALWAYS remain unchanged.

Is there a situation when the arterioles are the ONLY vessels being targeted to constrict? How about the veins? Nonetheless, even if there was solitary arteriolar constriction TPR would still remain unchaged assuming the ''equal dilation for every constriction" theory is sound. Resistance is pretty much soley determined by changes in radius. Thus, if you have no net radius chage then TRP can't EVER change and the slope of the vascular function curve will not change either.

Unless you have a vasculitis or deposit buildup [basically anything pathological other than physiological arteriolar constriction] of some sort, then I can't think of any other way TPR will change----assuming Guyton's "equal dilation for every constriction" theory is sound.


The essence of my concern are these questions:

1) Since the arterioles are constricted after intravenous injection of epinephrine in Guyton's experiment, then why doesn't TPR [and thus the slope of the VFC] change. It seems to be the rule in texts, that as the arterioles constrict TPR increases.

2) Since epinephrine is injected intravenously ALL vessels are attempting to constrict at the same time, as Guyton states. Thus, how are the arterioles able to constrict in the first place if all vessels are attempting to constrict simultaneously from the epinephrine, since blood is incompressible?

3)I am assuming the "equal dilation for every constriction" ideal is the reason TPR does not change---is this a false assumption? If it is false, then what is keeping the TPR from changing since the arterioles are constricting?



What do you think?