One of the most important factors responsible for stroke volume is the extent of cardiac filling during diastole.

With other factors equal, stroke volume increases as cardiac filling increases.

The stroke volume is determined by three parameters: (1) contractility, (2) preload, and (3) afterload.

Cont

Contractility is the amount of force exerted at a given muscle fiber length.

Preload is defined as the ventricular wall tension at the end of diastole and is quantified by the left ventricular end-diastolic pressure (LVEDP). Afterload is the ventricular wall tension during systole and is determined by the mean arterial pressure. 

Figure 3–4A illustrates how increasing muscle preload will increase the extent of shortening during a subsequent contraction with a fixed total load.

Recall from the nature of the resting length–tension relationship that an increased preload is necessarily accompanied by increased initial muscle fiber length.

When a muscle starts from a greater length, it has more distance to shorten before it reaches the length at which its tension-generating capability is no longer greater than the load on it. The same behavior is exhibited by cardiac muscle cells when they are actually operating in the ventricular wall. Increased ventricular preload (i.e., diastolic filling) increases both end-diastolic volume and stroke volume almost equally, as illustrated in Figure 3–4B.

The precise relationship between cardiac diastolic filling pressure and end-diastolic volume has especially important physiological and clinical consequences. Although the actual relationship is somewhat curvilinear, especially at very high filling pressures, it is nearly linear over the normal operating range of the normal heart. The low slope of this relationship indicates the substantial compliance of the normal ventricle during diastole (e.g., a change in filling pressure of only 1 mm Hg normally will change end-diastolic volume by approximately 25 mL). As will be discussed in Chapter 11, one major form of cardiac failure is called “diastolic failure” and is characterized by a low ventricular compliance and a decidedly abnormal relationship between cardiac filling pressure and end-diastolic volume. 4

It should be noted in Figure 3–4A that increasing preload increases initial muscle length without significantly changing the final length to which the muscle shortens against a constant total load. Thus, increasing ventricular filling pressure increases stroke volume, primarily by increasing end-diastolic volume. As shown in Figure 3–4B, this is not accompanied by a significant alteration in end-systolic volume.

Effect of Changes in Ventricular Afterload

As stated previously, systemic arterial pressure is usually taken to be the left ventricular “afterload.” A slight complication is that arterial pressure varies between a diastolic value and a systolic value during each cardiac ejection. Usually, however, we are interested in mean ventricular afterload and take this to be mean arterial pressure.

 Figure 3–5A shows how increased afterload, at constant preload, has a negative effect on cardiac muscle cell shortening. Again, this is simply a consequence of the fact that muscle cannot shorten beyond the length at which its peak isometric tension-generating potential equals the total load on it. Thus, shortening must stop at a greater muscle length when afterload is increased.

Normally, mean ventricular afterload is quite constant because mean arterial pressure is held within tight limits by the cardiovascular control mechanisms described later. In many pathological situations such as hypertension and aortic valve obstruction, however, ventricular function is adversely influenced by abnormally high ventricular afterload. When this occurs, stroke volume may be decreased, as shown by the changes in the pressure–volume loop in Figure 3–5B. Under these conditions, note that stroke volume is decreased because end-systolic volume is increased.

The relationship between end-systolic pressure and end-systolic volume obtained at a constant preload but different afterloads is indicated by the dotted line in Figure 3–5B. In a normally functioning heart, the effect of changes in afterload on end-systolic volume (and therefore stroke volume) is quite small (approximately 0.5 mL/mm Hg). However, in what is termed “systolic cardiac failure,” the effect of changes in afterload on end-systolic volume is greatly exaggerated such that a small increase in arterial pressure can significantly reduce stroke volume. Thus, the slope of this line can be used clinically to assess the systolic function of the heart, as discussed further in Chapter 11.

Effect of Changes in Cardiac Muscle Contractility

Recall that activation of the sympathetic nervous system results in release of norepinephrine from cardiac sympathetic nerves, which increases contractility of the individual cardiac muscle cells. This results in an upward shift of the peak isometric length–tension curve. As shown in Figure 3–6A, such a shift will result in an increase in the shortening of a muscle contracting with constant preload and total load. Thus, as shown in Figure 3–6B, the norepinephrine released by sympathetic nerve stimulation will increase ventricular stroke volume by decreasing the end-systolic volume, without directly influencing the end-diastolic volume.

The term ejection fraction is a clinically useful variable used to assess cardiac muscle contractility. It is the fraction of the blood in the ventricle at the end of diastole that is ejected during systole. It is defined as the ratio of stroke volume (SV) to end-diastolic volume (EDV):

Because increased myocardial contractility causes an increase in ventricular ejection fraction, measurements of ejection fraction are often used clinically to assess the state of myocardial contractility. 5

In addition to this change in the extent of myocyte shortening, an increase in contractility will also cause an increase in the rates of myocyte tension development and of shortening. This will result in an increase in the rate of isovolumetric pressure development and the rate of ejection during systole.

The major influences on cardiac output are summarized in Figure 3–7. The heart rate is controlled by chronotropic influences on the spontaneous electrical activity of SA nodal cells. Cardiac parasympathetic nerves have a negative chronotropic effect, and sympathetic nerves have a positive chronotropic effect on the SA node. Stroke volume is controlled by influences on the contractile performance of the ventricular cardiac muscle—in particular, its degree of shortening in the afterloaded situation. The 3 distinct influences on stroke volume are contractility, preload, and afterload. Increased cardiac sympathetic nerve activity tends to increase stroke volume by increasing the contractility of the cardiac muscle. Increased arterial pressure tends to decrease stroke volume by increasing the afterload on cardiac muscle fibers. Increased ventricular filling pressure increases end-diastolic volume, which tends to increase stroke volume through the Starling law.

It is important to recognize at this point that both the heart rate and stroke volume are subject to more than one influence. Thus, the fact that increased contractility tends to increase stroke volume should not be taken to mean that, in the intact cardiovascular system, stroke volume is always high when contractility is high. Following blood loss caused by hemorrhage, for example, stroke volume may be low in spite of a high level of sympathetic nerve activity and increased contractility. The only other possible causes for low stroke volume are high arterial pressure and low cardiac filling pressure. Because arterial pressure is normal or low following hemorrhage, the low stroke volume associated with severe blood loss must be (and is) the result of low cardiac filling pressure.

Cardiac Function Curves

One very useful way to summarize the influences on cardiac function and the interactions between them is by cardiac function curves such as those shown in Figure 3–8.

In this case, cardiac output is treated as the dependent variable and is plotted on the vertical axis in Figure 3–8, while cardiac filling pressure is plotted on the horizontal axis. 6

Different curves are used to show the influence of alterations in cardiac sympathetic nerve activity. Thus, Figure 3–8 shows how the cardiac filling pressure and the activity level of cardiac sympathetic nerves interact to determine cardiac output. When the cardiac filling pressure is 2 mm Hg and the activity of cardiac sympathetic nerves is normal, the heart will operate at point A and will have a cardiac output of 5 L/min. Each single curve in Figure 3–8 shows how cardiac output would be changed by changes in cardiac filling pressure if cardiac sympathetic nerve activity were held at a fixed level. For example, if cardiac sympathetic nerve activity remained normal, increasing cardiac filling pressure from 2 to 4 mm Hg would cause the heart to shift its operation from point A to point B on the cardiac function diagram. In this case, cardiac output would increase from 5 to 7 L/min solely as a result of the increased filling pressure (the Starling law). If, on the other hand, cardiac filling pressure were fixed at 2 mm Hg while the activity of cardiac sympathetic nerves was moderately increased from normal, the heart would change from operating at point A to operating at point C. Cardiac output would again increase from 5 to 7 L/min. In this instance, however, cardiac output does not increase through the length-dependent mechanism because cardiac filling pressure did not change. Cardiac output increases at constant filling pressure with an increase in cardiac sympathetic activity for 2 reasons. First and most importantly, increased cardiac sympathetic nerve activity increases the heart rate. Second, increased sympathetic nerve activity increases stroke volume by increasing cardiac contractility. 7

Cardiac function graphs thus consolidate knowledge of many mechanisms of cardiac control and are most helpful in describing how the heart interacts with other elements in the cardiovascular system. Furthermore, these graphs reemphasize the important point that a change in cardiac filling pressure alone will have a very potent effect on cardiac output at any level of sympathetic activity.