Preload: Frank-Starling Mechanism

An increased venous return increases the end-diastolic or filling volume of the ventricles. The greater the end-diastolic volume, the more the ventricular muscle fibers are stretched. This load, or stretch, placed on myocardial fibers just before contraction is the heart’s preload. According to the Frank-Starling law, an increase in preload causes myocardial fibers to contract with greater force and eject a greater stroke volume (see Chapter 17). Within physiological limits, the ventricles pump all the blood they receive without allowing it to dam in the atria and veins. Figure 20-1 is a Frank-Starling curve, also known as a cardiac function curve.

Another mechanism related to muscle fiber stretch also influences cardiac output. When increased venous return stretches the right atrial wall, it stretches the sinoatrial node, increasing its impulse generation frequency by 10% to 20%.¹ Myocardial fiber stretch increases cardiac output by increasing both contraction force and heart rate, although the Frank-Starling mechanism is the most important in this regard.

In clinical practice, measurement of right atrial and left atrial pressures is used to estimate the preload. These pressures represent the right and left ventricular “loading” or “filling” pressures and are equivalent to right ventricular end-diastolic pressure (RVEDP) and left ventricular end-diastolic pressure (LVEDP). These preload pressures are indicators of muscle fiber length. However, high preload pressures may not significantly increase muscle fiber length if ventricular compliance is abnormally low or ventricular expansion is restricted by high external pressure, as might occur with pericardial fluid buildup or high intrapleural pressures during mechanical ventilation. Such factors must be considered when atrial pressures are used to assess ventricular preload.

Afterload

Afterload can be thought of as ventricular outflow resistance; it is the resistance opposing ejection of the ventricular stroke volume into the pulmonary artery or the aorta. Clinical indicators of left and right ventricular afterload are mean arterial pressure (MAP) and mean pulmonary artery pressure (MPAP). Any factor that affects blood pressure affects afterload; for example, vasoconstriction increases afterload, and vasodilation decreases it.

The pumping effectiveness of the healthy heart is not influenced by afterload as much as it is by preload. Blood pressure (afterload) must increase to a very high level before stroke volume diminishes. For example, an abrupt increase in arterial resistance decreases the ventricle’s ejected stroke volume for the first few beats, causing higher volumes of blood to be left in the ventricles at the end of systole. As a result, blood flowing into the ventricles during diastole stretches myocardial fibers more than before. The increased stretch enhances the healthy ventricle’s contraction force, restoring the original stroke volume. In this way, the Frank-Starling mechanism helps the ventricle accommodate an increased afterload, maintaining a constant stroke volume. As one might predict, an increase in afterload increases myocardial work and oxygen consumption for a given cardiac output.

Contractility and Ejection Fraction

The force of myocardial muscle fiber contraction for a given preload and afterload is known as the heart’s contractility. In other words, the heart’s response to changes in preload while the afterload is constant is a measure of contractility. A heart with increased contractility produces a greater stroke volume for a given preload (filling pressure) than a heart with normal contractility. This means that the ventricle ejects a larger fraction of its end-diastolic volume as contractility increases—that is, the ejection fraction increases. Ejection fraction is thus a measure of ventricular contractility. The heart’s normal ejection fraction is approximately 60% of the end-diastolic volume under resting conditions; in strenuous exercise, it may increase to 90%.¹

The concept of contractility is shown in the Frank-Starling curves in Figure 20-2. These curves are also known as cardiac function curves. The greater the heart’s contractility, the greater is its workload and oxygen demand. Factors influencing the heart’s contractility are called inotropic factors. Positive inotropic factors increase the heart’s contractility; negative inotropic factors decrease contractility.

Venous Return Curves

As discussed earlier, the cardiovascular system consists of cardiac and vascular subdivisions. The Frank-Starling curve (see Figure 20-1) is relevant to the cardiac subdivision; it illustrates the relationship between cardiac output and right atrial pressure. The venous return curve (Figure 20-3) is relevant to the vascular subdivision; it illustrates the relationship between right atrial pressure and venous return. A positive feedback relationship exists between the cardiac and vascular subdivisions: In the cardiac subdivision, an increase in right atrial pressure causes an increase in cardiac output (Frank-Starling mechanism); in the vascular subdivision, an increase in cardiac output secondary to increased contractility causes a decrease in right atrial pressure, which enhances venous return.² At any given point in time, the right atrial pressure is common to both cardiac and vascular subdivisions, simultaneously playing a different role in each.

The venous return curve shows that if cardiac output were to suddenly fall to zero (as it would in cardiac arrest) and if all neural circulatory reflexes were abolished, right atrial pressure would increase to a maximum of about 7 mm Hg, reflecting the overall static equilibrium between venous and arterial pressures.¹ This hypothetical vascular equilibrium pressure established under static, no-flow conditions is called the mean circulatory filling pressure. The vascular equilibrium pressure in this hypothetical situation is lower than the simple average of pressures in venous and arterial vessels because the veins are highly distensible and serve as a large reservoir in which blood pools.

The mean circulatory filling pressure is determined by two major factors: the blood volume and intravascular space, or the size of the vascular “container.” The intravascular space is determined mainly by vessel diameter, which is a factor of (1) the elastic recoil force of the vessels and (2) vessel smooth muscle tone, or the degree of vasoconstriction present.³ When blood is circulating normally, the average pressure at the venous end of the systemic capillaries is about equal to the theoretical mean circulatory filling pressure.³ The difference between this pressure and right atrial pressure is the pressure gradient that drives venous return.¹ If the heart fails to pump all the blood it receives from the veins, blood dams up in the right atrium and increases its pressure, which decreases the pressure gradient that drives venous return. As a result, venous inflow of blood falls to match the failing heart’s reduced pumping capacity. On the other hand, if cardiac contractility increases and the heart pumps out more blood than it receives, right atrial pressure falls, increasing the pressure gradient that drives venous return.

If the heart pumps blood so vigorously that right atrial pressure falls below zero (see Figure 20-3), venous return and cardiac output stop rising. The reason for this phenomenon is that as the heart contracts more powerfully, it generates an increasingly greater subatmospheric pressure in the right atrium and the inferior vena cava, collapsing this great vein just before it enters the thoracic cavity; that is, the higher abdominal cavity pressure surrounding the vein caves in its walls just before it enters the chest. As a result, venous return and cardiac output cannot increase further.

Effect of Blood Volume and Arteriolar Resistance on Venous Return Curve

Figure 20-4 illustrates the effect of increased and decreased blood volume on the venous return curve. The mean circulatory filling pressure, hypothetically equal to intravascular pressure during circulatory standstill, depends only on vessel wall recoil (compliance) and blood volume. For a given vessel compliance, increased blood volume (hypervolemia) increases the mean circulatory filling pressure; decreased blood volume (hypovolemia) decreases mean circulatory filling pressure. Figure 20-4 illustrates this concept, showing mean circulatory filling pressures of 9 mm Hg for hypervolemia, 7 mm Hg for normovolemia, and 5 mm Hg for hypovolemia. In other words, the more the vascular space is filled, the “tighter” the vessels become; this increases the mean circulatory filling pressure and shifts the venous return curve up and to the right. Conversely, the less the vascular space is filled, the “looser” the system becomes, lowering the mean circulatory filling pressure and shifting the venous return curve down and to the left.

Figure 20-5 illustrates the effect of arteriolar resistance on the venous return curve. Because the arterioles contain only about 3% of the total blood volume, their constriction or dilation does not significantly affect mean circulatory filling pressure.⁴ Therefore, the venous return curves representing different arteriolar resistances in Figure 20-5 have different slopes but converge on the same mean circulatory filling pressure “hinge” point (7 mm Hg). (These curves assume that blood volume and vascular compliance remain constant.) Figure 20-5 shows that a decrease in arteriolar resistance allows more blood to flow through systemic capillaries, into the veins, and into the right atrium. This rotates the curve about its mean circulatory filling pressure hinge point (7 mm Hg) in an upward direction; the decrease in the curve’s slope denotes less resistance (higher cardiac output for a given right atrial pressure). Conversely, high arteriolar resistance decreases the amount of blood that can flow through systemic capillaries each minute and reduces blood return to the right atrium; this rotates the venous return curve around the same hinge point in a downward direction; the increased slope of the curve denotes greater resistance (lower cardiac output for a given right atrial pressure).

Effect of Contractility Changes

Figure 20-8 illustrates the effect of increased and decreased myocardial contractility on the cardiovascular system. Point A is the normal operating point. In a hypothetical situation in which only contractility increases (constant blood volume and vascular resistance), the cardiac function curve moves up and to the left, intersecting the venous return curve at point B. This point represents a new equilibrium in which the heart pumps more blood from the right atrium, decreasing right atrial pressure and increasing the gradient for venous return. Consequently, venous return increases to match the increased cardiac output. In the end, cardiac output and venous return are greater at a lower right atrial (preload) pressure, which is the hallmark of increased contractility.

Conversely, if myocardial contractility suddenly decreases (assuming a constant blood volume and vascular resistance), cardiac output decreases. The cardiac function curve moves down and to the right, intersecting the venous return curve at point C in Figure 20-8. This point represents a new equilibrium in which the heart pumps less blood than normal from the right atrium, and right atrial pressure increases. The resulting decrease in the venous return pressure gradient is consistent with the decreased cardiac output. In this situation, cardiac output and venous return are lower at a higher right atrial pressure, which is a hallmark of decreased contractility (e.g., congestive heart failure). (The term “congestive” refers to the congestion or pooling of blood in the veins.)

Effects of Blood Volume Changes

An increased blood volume (as occurs with intravenous fluid infusion) increases vascular pressures throughout the system; mean circulatory filling pressure increases, causing the venous return curve to shift up and to the right, intersecting the cardiac function curve at point B (Figure 20-9). Cardiac output increases, moving from point A to point B in Figure 20-9. In this way, cardiac output increases to accommodate the increased venous return; however, this increase does not represent greater contractility because the position of the cardiac function curve stays constant in this example. As venous blood flow into the heart increases, the heart responds according to the Frank-Starling law by contracting with greater force, but its ejection fraction does not change.

A sudden blood volume loss such as occurs with hemorrhage has the opposite effect. Venous pressures fall and myocardial fibers are less stretched; in accordance with the Frank-Starling law, cardiac output decreases. The venous return curve shifts down and to the left to a new equilibrium point (point C in Figure 20-9).

Effect of Peripheral Arteriolar Resistance Changes

An increased arteriolar resistance produces complex changes in the Guyton diagram because both cardiac and venous return curves shift simultaneously. To understand the general concept, it is helpful to consider the hypothetical effect of an increased arteriolar resistance alone, with the right atrial pressure and cardiac force of contraction remaining constant (Figure 20-10). Under such circumstances, an increased resistance would cause the venous return curve to rotate down and to the left, pivoting around its constant right atrial pressure hinge point (mean circulatory filling pressure) on the graph’s horizontal axis. At the same time, the cardiac function curve would shift down and to the right because at a constant right atrial pressure and force of contraction, the heart would pump less blood against a greater resistance or afterload. The right atrial pressure would stay constant in this hypothetical example because of proportional decreases in both cardiac output and venous return. The new equilibrium point B would be formed below the original point A.

However, Figure 20-10 artificially separates the effects of vascular resistance from the effects of subsequent compensatory factors. It does not take into account the normal physiological response of the healthy heart to an increase in afterload. As explained previously, an increased afterload raises the heart’s end-systolic volume, increasing the preload; in response, the Frank-Starling mechanism increases the healthy heart’s contracting force and stroke volume. The resulting increase in arterial pressure overcomes the increased arteriolar resistance and maintains the cardiac output at a normal level. However, if the heart has poor contractility and is already overstretched, an increased vascular resistance may induce acute cardiac failure.

Effect of Therapeutic Interventions

To anticipate how cardiovascular drugs and intravenous fluids affect the cardiac output and venous return curves, one must consider the effect of the intervention on each curve separately. To assess the effect of an intervention on the cardiac output curve, one need only answer the question: Does the intervention increase, decrease, or not affect the heart’s contractility? For example, drugs that increase sympathetic tone (e.g., epinephrine) or inhibit parasympathetic tone (e.g., atropine) or that increase intracellular calcium ion concentration (e.g., digitalis) increase the heart’s contractility and move the cardiac output curve up and to the left. Drugs that inhibit sympathetic tone (e.g., beta blockers) or block the cell membrane calcium ion channels (e.g., calcium channel blockers) decrease myocardial contractility and move the cardiac output curve down and to the left.

To assess the effect of an intervention on the venous return curve, one need only answer the question: Does the intervention change the relationship between intravascular space and the blood volume? Such an intervention entails a change either in blood volume (intravenous fluids or diuretic drugs) or in the vascular space (vasoconstrictor or vasodilator drugs). Intravenous fluid infusion would move the venous return curve up and to the right, which would increase the mean circulatory filling pressure and increase the cardiac output (it would intercept the cardiac output curve at a higher level). Diuretics would move the venous return curve down and to the left, which would decrease the mean circulatory filling pressure and cardiac output (it would intercept the cardiac output curve at a lower level). Vasodilator drugs would decrease the slope of the venous return curve, increasing the cardiac output for a given right atrial pressure (the venous return curve would intercept the cardiac output curve at a higher point). Vasoconstrictor drugs would have the opposite effect.

Normal Compensatory Response to Sudden Loss of Contractility

Acute myocardial infarction suddenly reduces the heart’s contractility and pumping ability (usually the left ventricle), and cardiac output acutely decreases. Momentarily, blood flows into the left ventricle at a higher rate than it is pumped out, causing blood to dam up in the left atrium, the pulmonary vasculature, and ultimately the right ventricle and atrium. Increased right atrial pressure is reflected throughout the systemic venous circulation. A new low-flow state develops in which cardiac output and venous return are again equal, with higher venous pressures and lower arterial pressures than normal. This situation, called acute uncompensated heart failure, is shown in Figure 20-11 (see point B).

The body’s immediate response is a massive sympathetic nervous discharge. Sympathetic stimulation is helpful in two ways: (1) it immediately increases the damaged heart’s contractility or inotropic state, and (2) it causes systemic arterial and venous vasoconstriction. Improved contractility shifts the cardiac function curve slightly up and to the left. At the same time, vasoconstriction “tightens” the blood vessels, shifting the venous return curve up and to the right. Over the long-term, blood volume increases because the kidney conserves water in response to the chronically low blood pressure. The combination of (1) improved contractility, (2) vasoconstriction, and (3) renal fluid retention creates a new compensated equilibrium point (see point C in Figure 20-11). This is known as compensated heart failure. Cardiac output is restored to normal values, but this requires higher left ventricular filling pressures than