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

normal. As a result, the pressures in the pulmonary vasculature, right heart, and systemic veins are higher than normal. In compensated heart failure, a higher right atrial pressure is required to achieve a cardiac output of 5 L per minute (see point C in Figure 20-11) than in the normal heart (see point A).

Figure 20-12, A, shows a sudden reduction in cardiac output to 2.5 L per minute with subsequent increases in right atrial and venous pressures (compare with Figure 20-6). Figure 20-12, A, corresponds with point B on the graph in Figure 20-11. Figure 20-12, B, illustrates an improved pumping ability caused by the inotropic influence of sympathetic stimulation and increased blood volume. This compensated state corresponds with point C in Figure 20-11.

Derived Variables

Other physiologically important information can be calculated from directly measured hemodynamic variables. Table 20-2 lists these calculated hemodynamic variables.

The cardiac index (CI) is the cardiac output divided by the body surface area (BSA) in square meters. BSA is related to height and weight and is correlated with body mass (see the DuBois body surface area chart in Appendix IV). People of different sizes can be compared by indexing the cardiac output to BSA. For example, a basketball player who is 7 feet tall has a higher cardiac output than an average person who is 5 feet, 10 inches tall. Both individuals have similar CIs, which are obtained by dividing cardiac output by BSA. A CI less than 2.5 L/min/m² indicates a generalized state of low blood flow and poor peripheral circulation, implying poor myocardial contractility or greatly reduced blood volume.⁶

The stroke volume is the cardiac output divided by the heart rate. Abnormally low contractility reduces stroke volume. Very high heart rates also may reduce the stroke volume because the ventricles have inadequate filling time during diastole. The stroke volume index relates stroke volume to body size. Similar to a low CI, a low stroke volume index implies poor myocardial contractility.

Systemic vascular resistance (SVR) and the systemic vascular resistance index (SVRI) are indicators of left ventricular afterload. The left ventricle must overcome SVR to eject its stroke volume. Increased SVR is caused by arteriolar vessel constriction; decreased SVR is caused by vasodilation. Likewise, PVR and the pulmonary vascular resistance index (PVRI) are indicators of right ventricular afterload and are caused by changes in pulmonary vessel diameters. The SVRI and PVRI calculations use CI rather than cardiac output in the denominator.

The driving pressures that produce blood flow through systemic and pulmonary circulations are first calculated to determine SVR and PVR. These pressure gradients are divided by the blood flow—that is, the cardiac output. This method works because resistance is measured in terms of pressure per unit of flow (mm Hg/L/min).

The systemic circulation driving pressure is equal to the difference between MAP (the beginning point of the systemic circulation) and mean right atrial pressure (the end point of the systemic circulation). This difference divided by cardiac output yields SVR in mm Hg/L/min. Multiplying the SVR by 80 changes mm Hg/L/min to centimeter-gram-second (CGS) units of measure, commonly designated in the clinical setting as dynes • sec • cm⁻⁵ (see Table 20-2 and Chapter 6).

The driving pressure for the pulmonary circulation is also the difference between the circulation’s beginning pressure (MPAP) and ending pressure (PCWP). Dividing this difference by the cardiac output and multiplying by 80 gives PVR in CGS resistance units.

Left and right ventricular stroke work indices indicate left and right ventricular contractility and oxygen consumption. Stroke work index is a measure of how hard the ventricle must contract to move blood through the vascular system. In terms of classic physics, work is done when a force moves a mass a given distance (work = force × distance). In the heart, force is the average pressure the ventricle generates, and distance is the volume of blood ejected (stroke volume). The differences between the ventricles’ end-diastolic pressures and their corresponding MAPs are the average pressures the ventricles must generate to eject their stroke volumes during contraction. Clinical indicators of end-diastolic pressures for the right and left ventricles are the right atrial pressure and PCWP. The pressure that the left ventricle generates during contraction is the numerical difference between MAP and PCWP, and for the right ventricle, it is the difference between MPAP and the right atrial pressure. Multiplying both pressure differences by the stroke indices produces the stroke work index for the left and right ventricles. The multiplication of the stroke work index by 0.0136 converts the units to gram-meters/m²/beat, which is the standard unit used in medicine to express cardiac work (see Table 20-2).

If the left ventricle loses its contractility, it cannot perform much work because it cannot pump much blood; the left ventricular stroke work index decreases. At the same time, myocardial oxygen consumption decreases because the heart performs less work. Table 20-3 summarizes the clinical hemodynamic indicators of the heart’s preload, afterload, and contractility.

Capillary Hydrostatic Pressure

PCWP is the pressure in the pulmonary capillaries that tends to force fluid into the interstitial space. Normally, this force of 6 to 12 mm Hg is opposed by capillary osmotic forces, and with the help of lymphatic removal of interstitial fluid, pulmonary edema is prevented.

When the PCWP increases to greater than 18 mm Hg, early clinical signs of pulmonary edema generally appear on the chest x-ray image. At a PCWP greater than 25 mm Hg, the chest x-ray film shows obvious evidence of pulmonary edema.⁶ The PCWP provides valuable information about the effects of intravenous fluid infusions in hemodynamically unstable patients.

Left Ventricular Preload

Ideally, the PCWP equals the left atrial pressure, which equals the left ventricular end-diastolic pressure (LVEDP). LVEDP is normally proportional to the left ventricular end-diastolic volume (LVEDV). The true concept of preload refers to fiber length, not ventricular pressure. A reasonable assumption is that LVEDV is directly related to muscle fiber length. However, increased ventricular diastolic pressure may not translate into increased volume or increased fiber length in abnormal circumstances. For example, any factor that restricts ventricular expansion during diastole alters the relationship between pressure and volume. Such factors include (1) an already overstretched, distended ventricle; (2) pericardial tamponade; (3) myocardial infarction scaring (stiff ventricle); and (4) the increased pressure surrounding the heart during positive pressure mechanical ventilation, especially in the presence of high levels of positive end expiratory pressure (PEEP). In these cases, LVEDP is elevated, which increases left atrial pressure and PCWP; however, these high pressures reflect a restriction to the ability of the left ventricle to expand, not increased volume or fiber length.

Clinical Focus 20-2   Interpretation of Pulmonary Capillary Wedge Pressure in the Presence of Mechanical Ventilation and Positive End Expiratory Pressure

The relationship between PCWP and left ventricular filling pressure is especially important in mechanically ventilated patients with PEEP. True left ventricular filling pressure is the pressure distending the ventricular wall—that is, the pressure inside the ventricle minus the pressure outside the ventricle. The pressure outside the ventricle is the surrounding intrathoracic pressure. Figure 20-16, A, represents normal, spontaneous breathing conditions when LVEDP is 6 mm Hg. The pulmonary artery catheter senses this pressure as PCWP of 6 mm Hg. The intrathoracic pressure is −5 mm Hg, producing a transmural (across the wall) filling pressure of 11 mm Hg. In Figure 20-16, B, mechanical ventilation and PEEP have increased mean intrathoracic pressure from −5 mm Hg to +10 mm Hg for a total increase of 15 mm Hg. About half of this pressure increase (7.5 mm Hg) is transmitted into the ventricle, increasing LVEDP from 6 mm Hg to 13.5 mm Hg. The pulmonary artery catheter measures PCWP of 13.5 mm Hg, an apparent increase in filling pressure. However, the transmural filling pressure is only 3.5 mm Hg, an actual decrease in filling pressure compared with spontaneous breathing. (The transmural filling pressure is obtained by subtracting the new intrathoracic pressure [10 mm Hg] from LVEDP [13.5 mm Hg].) In this case, increased PCWP inaccurately signaled an increase in left ventricular filling pressure. PCWP must be interpreted with caution when mechanical ventilation with PEEP is used. A clinical rule of thumb is to subtract about one half (with normal lung compliance) to one fourth (with low lung compliance) of PEEP from PCWP to estimate true filling pressure. Generally, this adjustment needs to be made only when PEEP is greater than 15 cm H₂O.

Abnormal Preload

If PCWP is elevated, clinicians should investigate factors in the patient that cause high preload, such as hypervolemia and ventricular failure. High intrapleural pressure induced by mechanical ventilation also could be a cause of elevated PCWP, although this does not increase the preload. If hypervolemia is the cause, measures that reduce blood volume are needed, such as administration of diuretic drugs. Ventricular failure may be addressed by at least two different approaches: (1) administration of vasodilator drugs to reduce ventricular afterload and (2) administration of drugs that increase contractility (inotropic drugs). Both drugs improve pumping effectiveness and reduce preload. If high mechanical ventilation pressures are the problem, measures to reduce mean intrapleural pressures are taken. Similarly, when PCWP is low, especially if accompanied by a low cardiac output, intravenous fluids should be infused. Figure 20-20 illustrates these general principles of management.

Abnormal Afterload

If SVR and SVRI are elevated, the patient is examined to discover the presence of factors that increase afterload, e.g., vasoconstriction increases SVR, which increases ventricular afterload. The likely cause of vasoconstriction must be identified next. Sympathetic vasoconstriction is a compensatory response to a decrease in cardiac output and blood pressure.

Clinical Focus 20-3   Differentiating Myocardial Infarction from Pulmonary Embolus

An elderly woman is brought back from surgery after repair of a fractured femur. Her course was uneventful until 8 hours later when she developed severe shortness of breath and central chest pain. She is now very anxious and breathes with large tidal volumes and a rapid respiratory rate. She is admitted to the intensive care unit where pulmonary artery and systemic arterial catheters are inserted. Monitoring data from the pulmonary artery catheter are as follows:

Right atrial pressure = 20 mm Hg

Pulmonary artery pressure = 52/30 mm Hg

MPAP = 45 mm Hg

PCWP = 6 mm Hg

Cardiac output = 5 L/min

Other vital signs are as follows:

Heart rate = 128 beats/min

Respiratory rate = 33 breaths/min

Blood pressure = 115/88 mm Hg

Are these findings consistent with a myocardial infarction and acute left heart failure?

Discussion

Myocardial infarction and pulmonary embolus often produce similar signs and symptoms: central chest pain, dyspnea, and respiratory distress. Myocardial infarction reduces ventricular contractility and stroke volume. The condition is expected to cause blood to dam up in the left atrium, which should produce increased PCWP. The high PCWP should be transmitted to the pulmonary artery, increasing pulmonary artery pressure.

A large pulmonary embolus pumped into the pulmonary artery would lodge in an arterial branch, blocking blood flow. This condition would also increase pulmonary artery pressure because it creates resistance to right ventricular output. However, pressure downstream from the embolus would not be elevated; it may actually be decreased if overall blood flow is decreased. Pulmonary embolus should increase pulmonary artery pressure but not PCWP. (PCWP is actually left atrial pressure, downstream from the embolus.)

From the hemodynamic data, you know this patient has a pulmonary problem, not a left-sided cardiac problem. A myocardial infarction cannot be causing this patient’s symptoms and hemodynamic abnormalities. A highly significant feature of the hemodynamic data is the difference between pulmonary artery diastolic pressure and PCWP (30 mm Hg − 6 mm Hg = 24 mm Hg). These two pressures are normally almost identical. This high pressure difference shows that PVR is high. Calculation of PVR confirms this:

PVR=([MPAP−PCWP]×80)÷Cardiac outputPVR=([45−6]×80)÷5PVR=624 dynes • sec • cm−5

A normal PVR is 100 to 250 dynes • sec • cm⁻⁵. Anticoagulant and possibly clot-dissolving drugs are indicated for this patient. Oxygen therapy and pain medication are also needed.

Both left ventricular failure and severe blood loss may decrease cardiac output and blood pressure; either condition can result in increased SVR.

In left ventricular failure, the increased afterload imposed by vasoconstriction increases myocardial work and oxygen demand, possibly worsening ventricular failure. Such circumstances call for vasodilator drugs to better balance the heart’s oxygen supply and demand.5,6 If the resistance to ejection is reduced, the percentage of ventricular volume ejected for a given contraction force increases without increasing oxygen demand. Although vasodilators decrease SVR, the subsequent increase in stroke volume and cardiac output tend to prevent a further fall in blood pressure. However, if blood pressure decreases after vasodilation, infusion of intravenous fluids may be necessary to maintain adequate preload and cardiac output.⁵ When SVR is reduced and fluids are infused, inotropic drugs can be administered cautiously to increase myocardial contractility if necessary. The benefits of drugs that increase contractility must be weighed against the increased work and oxygen requirement this places on the myocardium; it may be appropriate to use negative inotropic drugs to decrease contractility and myocardial oxygen demand.⁵ If increased SVR is caused by blood loss and hypovolemia, administration of intravenous fluids and possibly blood is indicated. Restoration of the blood volume eliminates compensatory vasoconstriction.

Abnormally low SVR and SVRI are caused by excessive vasodilation. The resulting decrease in blood pressure leads to underperfused and underoxygenated tissues. Coronary perfusion may be decreased, and cause myocardial ischemia and a reduced cardiac output. In this case, vasopressor drugs are needed to induce vasoconstriction. Perfusion pressure and oxygen delivery are increased to vital organs such as the heart, brain, liver, and kidneys.

Massive sepsis-induced vasodilation (septic shock) presents a special problem because it may not respond to conventional vasoconstrictors. Overproduction of nitric oxide by the vascular endothelium is an important mechanism of vasodilation in septic shock.⁷ Nitric oxide synthase inhibitors (agents that inhibit nitric oxide production) have been investigated for their potential role in treating patients with septic shock, but studies have yielded controversial results.

Abnormal Contractility

A low left ventricular stroke work index and low cardiac output indicate abnormally low myocardial contractility. Myocardial ischemia and myocardial infarction decrease cardiac contractility. Myocardial ischemia is caused by inadequate coronary blood flow because of either low perfusion pressure or coronary artery occlusion.

Myocardial infarction means functional heart muscle mass is reduced, which decreases contractility. The initial approach to this problem is generally intravenous fluid infusion if fluid overload and pulmonary edema are not present.⁸ In some failing hearts, PCWP may need to be maintained above normal levels to sustain an adequate cardiac output.⁵ On the other hand, if cardiogenic pulmonary edema is present, diuretics may be required to reduce fluid volume; diuretics are especially indicated in chronic heart failure in which compensatory renal fluid retention results in hypervolemia. After fluid volume has been optimized, afterload-reducing agents, or vasodilator drugs, are used to reduce myocardial work and oxygen requirements. Inotropic drugs may then be administered to increase contractility if intravascular fluid volume is adequate. The larger the myocardial infarction, the less effective are inotropic drugs because less functional myocardium is available to respond to the inotropic drug. A major concern in administration of inotropic drugs is that these agents may worsen myocardial ischemia by increasing myocardial work and oxygen demand.⁹ Afterload must be reduced and intravascular volume optimized before driving the heart with inotropic drugs. An increase in the ischemic heart’s contractility when preload is low may precipitate or further extend myocardial infarction.^9,10 Inotropic drugs that also have peripheral vasodilator effects lessen this risk; these drugs include dobutamine (Dobutrex), amrinone (Inocor), and milrinone (Primacor). The intraaortic balloon pump (IABP) may be beneficial in reducing afterload in this situation (see Clinical Focus 20-5 and Figure 20-21).

Patients with myocardial ischemia may benefit from negative rather than inotropic drugs because these agents reduce myocardial work and oxygen requirements. For the same reason, these patients also may benefit from drugs that reduce the heart rate. Such drugs include beta-receptor and calcium channel–blocking agents. These drugs produce some degree of vasodilation, lessening the decrease in stroke volume that would otherwise be associated with reduced contractility.

Drugs that dissolve blood clots (fibrinolytic therapy) improve the survival of patients with acute coronary artery occlusion, especially if the drug is given within 2 hours of the occlusion.¹¹ If given early enough, these drugs restore blood flow to the ischemic area of the heart before infarction can occur. Fibrinolytic intravenous drugs include tissue plasminogen activator (tPA) and streptokinase.

Other causes of decreased myocardial contractility include electrolyte (particularly potassium and calcium ions) and acid-base imbalances. Treatment involves infusing appropriate electrolytes and correcting acid-base disturbances. Oxygen administration is also essential to maximize myocardial oxygenation. Figure 20-20 provides the general principles of management based on hemodynamic information. Table 20-4 lists expected hemodynamic values in specific clinical conditions. Table 20-5 lists examples of drugs that alter hemodynamic values.

Clinical Focus 20-6   Therapeutic Options for Abnormal Hemodynamic Conditions

Case 1

A 60-year-old man comes into the emergency department complaining of severe chest pain. He has a medical history of a myocardial infarction that occurred 3 years ago. He is pale, sweating, and anxious. He seems to be in no respiratory distress. His vital signs are as follows:

Blood pressure: 130/80 mm Hg

Heart rate: 100 beats/min

Respiratory rate: 16 breaths/min

The electrocardiogram findings show signs of an acute myocardial infarction, and he is admitted to the intensive care unit. Several hours later, his blood pressure decreases to 100/75 mm Hg, and his heart rate increases to 125 beats per minute. His skin is cool and clammy, and his respiratory rate is 22 breaths per minute. You now hear fine, crackling breath sounds over both lung fields with your stethoscope. A pulmonary artery catheter is inserted, and the following data are gathered:

Right atrial pressure: 12 mm Hg

Pulmonary artery pressure: 42/25 mm Hg

MPAP: 31 mm Hg

PCWP: 23 mm Hg

Cardiac output: 3.5 L/min

Systemic blood pressure: 100/75 mm Hg

Room air arterial blood gas values are as follows:

pH = 7.48

PCO₂ = 33 mm Hg

HCO₃⁻ = 24 mEq/L

PaO₂ = 65 mm Hg

SaO₂ = 0.92

Hemoglobin = 14 g/dL

BSA = 1.75 m²

What is your interpretation?

Discussion

This patient is experiencing acute left ventricular pump failure. He does not have a severe oxygen transfer problem in the lung as evidenced by the PaO₂ and F_IO₂ values. The cool, clammy skin is a clinical sign of hypoperfusion. The decrease in blood pressure and increased heart rate mean the heart’s pumping efficiency is worsening; an increased rate is needed to sustain the cardiac output because stroke volume is decreasing. Rapid heart rates are dangerous in cases of myocardial ischemia because the decreased diastolic time leads to decreased coronary perfusion. Fine, crackling breath sounds are associated with pulmonary edema; this is consistent with left ventricular failure and damming of blood in the pulmonary capillaries. The following hemodynamic data confirm these suspicions:

High PCWP: Left ventricular contractility loss, pump failure, pulmonary edema of cardiac origin

CI: 3.5 ÷ 1.75 m² = 2.0 L/min/m² (subset IV in Figure 20-17, consistent with acute left heart failure)

PVR: (31 − 23) ÷ 3.5 = 2.29

2.29 × 80 = 183.2 dynes • sec • cm⁻⁵ (normal)

Left heart failure, not abnormal PVR, is causing the high pulmonary artery pressure; left heart failure also accounts for the increased right atrial pressure.

Stroke index: Stroke volume/BSA = (3500 mL/min ÷ 125) ÷ 1.75 m² = 16 mL/m²

Left ventricular stroke work index: (83.3 − 23) × 16 × 0.0136 = 13.1 g-m/m²/beat

Low left ventricular stroke work index confirms decreased left ventricular contractility (see Table 20-2).

SVR: (83.3 − 12) ÷ 3.5 × 80 = 1630 dynes • sec • cm⁻⁵

High SVR is consistent with systemic vasoconstriction, a compensatory response to decreased cardiac output; this increases myocardial oxygen consumption.

Oxygen delivery is as follows:

Cardiac output×([Hemoglobin×1.34×SaO2]+[PaO2×0.003])×10=3.5×(17.26+0.195)×10=611mL/min

Normal oxygen delivery is about 1000 mL per minute (see Chapter 7); the low oxygen delivery in this case is mainly a function of the low cardiac output. Your main goal is to increase oxygen delivery; although you need to administer oxygen, the main method for increasing oxygen delivery focuses on the cardiovascular system. Your general goals with regard to the cardiovascular system include the following:

1. Decrease myocardial work and oxygen requirements, while improving cardiac output—you must decrease SVR (afterload) and therefore will administer vasodilators.

2. Increase myocardial contractility—after reducing afterload, you may administer inotropic drugs to increase cardiac output further without overworking the heart.

3. Decrease PCWP to allow resolution of pulmonary edema and improve oxygenation—therapy administered in the first two steps addresses this goal. Improved pumping effectiveness decreases left atrial and pulmonary vascular pressures.

Case 2

A 55-year-old woman is admitted to the hospital for a severe urinary tract infection. She has a normal blood pressure and a temperature of 101° F. She is placed on intravenous antibiotics and fluids. Several days later, she develops a respiratory rate of 30 breaths per minute and a temperature of 103° F. Her blood pressure is now 83/50 mm Hg. She appears to be in respiratory distress and has fine, crackling breath sounds. Chest x-ray shows evidence of pulmonary edema in both lungs. In the intensive care unit, a Swan-Ganz catheter is inserted, and the following data are obtained:

Cardiac output = 7.5 L/min

SVR = 500 dynes • sec • cm⁻⁵

CI = 4.5 L/min/m²

MAP = 61 mm Hg

PCWP = 6 mm Hg

Pulmonary artery pressure = 25/10 mm Hg

MPAP = 15 mm Hg

What type of problem is this patient experiencing, and why does she have pulmonary edema?

Discussion

The pulmonary edema is not caused by high pulmonary capillary pressures because PCWP is normal. Although CI is above normal, the patient has systemic hypotension; this is caused by low SVR (see Table 20-2 for normal values). Considering the history of her illness, you should suspect septic shock; the urinary tract infection has probably developed into a generalized septicemia, which explains the low SVR, high CI, and pulmonary edema. Bacterial endotoxins dilate the systemic vasculature, decreasing afterload and increasing cardiac output. These endotoxins also injure the alveolar capillary membrane, increasing its permeability. Even at normal capillary pressures, pulmonary edema is present; this edema may be called noncardiogenic edema or high permeability pulmonary edema. Treatment includes intravenous fluids to maintain blood pressure, antibiotics, and vasopressors.