Physiology 5th Ed.

RELATIONSHIPS BETWEEN CARDIAC OUTPUT AND VENOUS RETURN

It should be clear from the previous discussion that one of the most important factors determining cardiac output is left ventricular end-diastolic volume. In turn, left ventricular end-diastolic volume depends on venous return, which also determines right atrial pressure. Thus, it follows that there is not only a relationship between cardiac output and end-diastolic volume but also a relationship between cardiac output and right atrial pressure.

Cardiac output and venous return each can be examined separately as a function of right atrial pressure. These separate relationships also can be combined in a single graph to visualize the normal interrelationship between cardiac output and venous return (see Fig. 4-25). The combined graphs can be used to predict the effects of changes in various cardiovascular parameters on cardiac output, venous return, and right atrial pressure.

Cardiac Function Curve

The cardiac function curve or cardiac output curve, shown in Figure 4-26, is based on the Frank-Starling relationship for the left ventricle. The cardiac function curve is a plot of the relationship between cardiac output of the left ventricle and right atrial pressure. Again, recall that right atrial pressure is related to venous return, end-diastolic volume, and end-diastolic fiber length: As venous return increases, right atrial pressure increases, and end-diastolic volume and end-diastolic fiber length increase. Increases in end-diastolic fiber length produce increases in cardiac output. Thus, in the steady state, the volume of blood the left ventricle ejects as cardiac output equals or matches the volume it receives in venous return.

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Figure 4–26 Cardiac and vascular function curves. The cardiac function curve is cardiac output as a function of right atrial pressure. The vascular function curve is venous return as a function of right atrial pressure. The curves intersect at the steady state operating point (filled circle) where cardiac output and venous return are equal.

Increases in end-diastolic volume (i.e., right atrial pressure) produce increases in cardiac output by the Frank-Starling mechanism. However, this “matching” occurs only up to a point: When right atrial pressure reaches a value of approximately 4 mm Hg, cardiac output can no longer keep up with venous return and the cardiac function curve levels off. This maximum level of cardiac output is approximately 9 L/min.

Vascular Function Curve

The vascular function curve or venous return curve, shown in Figure 4-26, depicts the relationship between venous return and right atrial pressure. Venous return is blood flow through the systemic circulation and back to the right heart. The inverse relationship between venous return and right atrial pressure is explained as follows: Venous return back to the heart, like all blood flow, is driven by a pressure gradient. The lower the pressure in the right atrium, the higher the pressure gradient between the systemic arteries and the right atrium and the greater the venous return. Thus, as right atrial pressure increases, this pressure gradient decreases and venous return also decreases.

The knee (flat portion) of the vascular function curve occurs at negative values of right atrial pressure. At such negative values, the veins collapse, impeding blood flow back to the heart. Although the pressure gradient has increased (i.e., as right atrial pressure becomes negative), venous return levels off because the veins have collapsed.

Mean Systemic Pressure

The value for right atrial pressure at which venous return is zero is called the mean systemic pressure. It is the point at which the vascular function curve intersects the X-axis (i.e., where venous return is zero and right atrial pressure is at its highest value). Mean systemic pressure or mean circulatory pressure is the pressure that would be measured throughout the cardiovascular system if the heart were stopped. Under these conditions, pressure would be the same throughout the vasculature and, by our definition, would be equal to the mean systemic pressure. When pressures are equal throughout the vasculature, there is no blood flow, and therefore, venous return is zero (because there is no pressure gradient or driving force).

Two factors influence the value for mean systemic pressure: (1) the blood volume and (2) the distribution of blood between the unstressed volume and the stressed volume. In turn, the value for mean systemic pressure determines the intersection point (zero flow) of the vascular function curve with the X-axis.

Figure 4-27 reviews the concepts of unstressed volume and stressed volume and relates them to mean systemic pressure. The unstressed volume (thought of as the volume of blood that the veins can hold) is the volume of blood in the vasculature that produces no pressure. The stressed volume (thought of as the volume in the arteries) is the volume that produces pressure by stretching the elastic fibers in the blood vessel walls.

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Figure 4–27 Effect of changes in stressed volume on mean systemic pressure. Total blood volume is the sum of unstressed volume (in the veins) and stressed volume (in the arteries). Increases in stressed volume produce increases in mean systemic pressure.

image Consider the effect of changing blood volume on mean systemic pressure. When the blood volume ranges from 0 to 4 L, all of the blood will be in the unstressed volume (the veins), producing no pressure, and the mean systemic pressure will be zero. When blood volume is greater than 4 L, some of the blood will be in the stressed volume (the arteries) and produce pressure. For example, if the total blood volume is 5 L, 4 L is in the unstressed volume, producing no pressure, and 1 L is in the stressed volume, producing a pressure of approximately 7 mm Hg (on the graph, read mean systemic pressure as 7 mm Hg at a blood volume of 5 L).

  It now should be clear how changes in blood volume can alter the mean systemic pressure (see Fig. 4-26). If blood volume increases, the amount of blood in the unstressed volume will be unaffected (if it is already full), but the amount of blood in the stressed volume will increase. When stressed volume increases, mean systemic pressure increases and the vascular function curve and its intersection point with the X-axis shift to the right. If blood volume decreases, then stressed volume decreases, mean systemic pressure decreases, and the vascular function curve and its intersection point with the X-axis shift to the left.

image Redistribution of blood between the unstressed volume and the stressed volume also produces changes in mean systemic pressure. For example, if the compliance of the veins decreases (e.g., venoconstriction), the veins can hold less blood and blood shifts from the unstressed volume to the stressed volume. Although total blood volume is unchanged, the shift of blood increases the mean systemic pressure and shifts the vascular function curve to the right. Conversely, if the compliance of the veins increases (e.g., venodilation), the veins can hold more blood. Hence, the unstressed volume will increase, the stressed volume and mean systemic pressure will decrease and the vascular function curve shifts to the left.

In summary, increased blood volume and decreased compliance of the veins produce an increase in mean systemic pressure and shift the vascular function curve to the right. Decreased blood volume and increased compliance of the veins produce a decrease in mean systemic pressure and shift the vascular function curve to the left.

Slope of the Vascular Function Curve

If mean systemic pressure is fixed or constant, the slope of the vascular function curve can be changed by rotating it. The slope of the vascular function curve is determined by total peripheral resistance(TPR). Recall that TPR is determined primarily by the resistance of the arterioles. The effect of TPR on venous return and the vascular function curve is explained as follows (see Fig. 4-26):

image A decrease in TPR causes a clockwise rotation of the vascular function curve. A clockwise rotation means that, for a given right atrial pressure, venous return is increased. In other words, decreased resistance of the arterioles (decreased TPR) makes it easier for blood to flow from the arterial to the venous side of the circulation and back to the heart.

image An increase in TPR causes a counterclockwise rotation of the vascular function curve. A counterclockwise rotation means that, for a given right atrial pressure, venous return is decreased. In other words, increased resistance of the arterioles (increased TPR) makes it more difficult for blood to flow from the arterial to the venous side of the circulation and back to the heart.

Combining Cardiac and Vascular Function Curves

The interaction between cardiac output and venous return can be visualized by combining the cardiac and vascular function curves (see Fig. 4-26). The point at which the two curves intersect is the unique operating or equilibrium point of the system in the steady state. In the steady state, cardiac output and venous return are, by definition, equal at the point of intersection. Why then do the cardiac and vascular function curves go in opposite directions and why do they have opposite relationships with right atrial pressure?

The answers lie in the way the two curves are determined. The cardiac function curve is determined as follows: as right atrial pressure and end-diastolic volume are increased, there is increased ventricular fiber length, which leads to increased stroke volume and cardiac output. The higher the right atrial pressure, the higher the cardiac output—this is the Frank-Starling relationship for the heart.

The vascular function curve is determined as follows: as right atrial pressure is decreased, venous return increases because of the greater pressure gradient driving blood flow back to the heart. The lower the right atrial pressure, the higher the venous return.

Now, to the questions! We have established that cardiac and vascular function curves have opposite relationships with right atrial pressure. But how can this be true if cardiac output and venous return are always equal? When cardiac output and venous return are plotted simultaneously as a function of right atrial pressure, they intersect at a single value of right atrial pressure (see Fig. 4-26). At this one value of right atrial pressure, cardiac output equals venous return and, by definition, is the steady state operating point of the system. That one value of right atrial pressure satisfies both cardiac output and venous return relationships.

Combining these curves provides a useful tool for predicting the changes in cardiac output that will occur when various cardiovascular parameters are altered. Cardiac output can be altered by changes in the cardiac function curve, by changes in the vascular function curve, or by simultaneous changes in both curves. The basic premise of this approach is that, after such a change, the system will move to a new steady state. In the new steady state, the operating point at which the cardiac and the vascular function curves intersect will have changed. This new operating point tells what the new cardiac output and thenew venous return are in the new steady state.

Changes in cardiac output can be produced by any of the following mechanisms: (1) positive or negative inotropic effects that alter the cardiac function curve; (2) changes in blood volume or venous compliance that alter the vascular function curve by changing mean systemic pressure; and (3) changes in TPR that alter both the cardiac and vascular function curves.

Inotropic Effects

Inotropic agents alter the cardiac function curve (Fig. 4-28). Recall that positive inotropic agents cause an increase in contractility for a given end-diastolic volume (or right atrial pressure), and negative inotropic agents produce a decrease in contractility.

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Figure 4–28 Effects of positive inotropic agents (A) and negative inotropic agents (B) on the cardiac and vascular function curves. The solid lines show the normal relationships, and the dashed lines show changes. The circle intersecting the dashed line shows the new steady state operating point.

image The effect of a positive inotropic agent (e.g., ouabain, digitalis, or digoxin) on the cardiac function curve is shown in Figure 4-28A. Positive inotropic agents produce an increase in contractility, an increase in stroke volume, and an increase in cardiac output for any level of right atrial pressure. Thus, the cardiac function curve shifts upward, but the vascular function curve is unaffected. The point of intersection (the steady state point) of the two curves now has shifted upward and to the left. In the new steady state, cardiac output is increased and right atrial pressure is decreased. The decrease in right atrial pressure reflects the fact that more blood is ejected from the heart on each beat as a result of the increased contractility and increased stroke volume.

image Figure 4-28B shows the effect of a negative inotropic agent. The effect is just the opposite of a positive inotropic agent: There is a decrease in contractility and a decrease in cardiac output for any level of right atrial pressure. The cardiac function curve shifts downward, and the vascular function curve is unchanged. In the new steady state, cardiac output is decreased and right atrial pressure is increased. Right atrial pressure is increased because lessblood is ejected from the heart on each beat, due to decreased contractility and decreased stroke volume.

Effects of Changes in Blood Volume

Changes in blood volume alter mean systemic pressure and, thereby, alter the vascular function curve (Fig. 4-29).

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Figure 4–29 Effects of increased blood volume (A) and decreased blood volume (B) on the cardiac and vascular function curves. The solid lines show the normal relationships, and the dashed lines show changes. The circle intersecting the dashed line shows the new steady state operating point.

image The effects of increases in blood volume (e.g., transfusion) are shown in Figure 4-29A. Increases in blood volume increase the amount of blood in the stressed volume and, therefore, increase the mean systemic pressure. Mean systemic pressure is the point on the vascular function curve where venous return is zero. Increases in blood volume shift this intersection point to the right and, therefore, shift the curve to the right in a parallel manner. (The shift is parallel because there is no accompanying change in TPR, which determines the slope of the vascular function curve.) In the new steady state, the cardiac and vascular function curves intersect at a new point at which cardiac output is increased and right atrial pressure is increased.

image The effects of decreases in blood volume (e.g., hemorrhage) are shown in Figure 4-29B. The decrease in blood volume decreases the amount of blood in the stressed volume and mean systemic pressure, which shifts the vascular function curve to the left in a parallel manner. In the new steady state, cardiac output is decreased and right atrial pressure is decreased.

image Changes in venous compliance produce effects similar to those produced by changes in blood volume. Decreases in venous compliance cause a shift of blood out of the unstressed volume and into the stressed volume and produce changes similar to those caused by increases in blood volume, a parallel shift to the right. Likewise, increases in venous compliance cause a shift of blood into the unstressed volume and out of the stressed volume and produce changes similar to those caused by decreased blood volume, a parallel shift to the left.

Effects of Changes in Total Peripheral Resistance

Changes in TPR reflect changes in the degree of constriction of the arterioles. Such changes alter the extent to which blood is “held” on the arterial side of the circulation (i.e., in the stressed volume). Thus, changes in TPR alter both arterial blood pressure and venous return to the heart. For example, an increase in TPR, by restricting the flow of blood out of the arteries, produces an increase in arterial blood pressure and, concomitantly, a decrease in venous return.

The effects of changes in TPR on the cardiac and vascular function curves are, therefore, more complicated than those produced by changes in contractility or blood volume. Changes in TPR alter both curves: The cardiac function curve changes because of a change in afterload (arterial blood pressure), and the vascular function curve changes because of a change in venous return (Fig. 4-30).

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Figure 4–30 Effects of increased total peripheral resistance (TPR) (A) and decreased TPR (B) on the cardiac and vascular function curves. The solid lines show the normal relationships, and the dashed lines show the changes. The circle intersecting the dashed lines shows the new steady state operating point.

image The effects of an increase in TPR (i.e., constriction of the arterioles) are shown in Figure 4-30A. (1) Increases in TPR cause an increase in arterial pressure by “holding” blood in the arteries. This increase in arterial pressure produces an increase in afterload on the heart, which decreases cardiac output. The cardiac function curve shifts downward as a result of the increased afterload. (2) The increase in TPR produces a counterclockwise rotation of the vascular function curve. This rotation means that less blood returns to the heart for a given right atrial pressure—venous return is decreased. (3) The combination of these two changes is shown in Figure 4-30A. The curves intersect at a new steady state point at which both cardiac output and venous return are decreased.

  In the figure, right atrial pressure is shown as unchanged. Actually, the final effect of increased TPR on right atrial pressure is not predictable because TPR has different directional effects via the cardiac and vascular function curves. An increase in TPR decreases cardiac output, which increases right atrial pressure (less blood is pumped out of the heart). And, an increase in TPR decreases venous return, whichdecreases right atrial pressure (less flow back to the heart). Depending on the relative magnitude of the effects on the cardiac and vascular function curves, right atrial pressure can be slightly increased, slightly decreased, or unchanged. The figure shows it as unchanged—the compromise position.

image The effects of a decrease in TPR (i.e., dilation of the arterioles) are shown in Figure 4-30B. (1) Decreases in TPR cause a decrease in arterial pressure and a decrease in afterload, causing the cardiac function curve to shift upward. (2) The decrease in TPR produces a clockwise rotation of the vascular function curve, which means that more blood returns to the heart for a given right atrial pressure—venous return is increased. The curves intersect at a new steady state point at which both cardiac output and venous return are increased.

  In the figure, right atrial pressure is shown as unchanged. However, the effect of decreased TPR on right atrial pressure is not easily predicted because a change in TPR has different effects via the cardiac and vascular function curves. A decrease in TPR increases cardiac output, which decreases right atrial pressure (more blood is pumped out of the heart). And a decrease in TPR increases venous return, whichincreases right atrial pressure (increased flow back to the heart). Depending on the relative magnitude of the effects, right atrial pressure can be slightly increased, slightly decreased, or unchanged. In the figure, it is shown as the compromise, or unchanged.