Control of stroke volume

Many factors contribute to the regulation of stroke volume. Factors discussed in this section include:

• Length of diastole

• Venous return (preload)

• Contractility of the myocardium

Two important concepts to keep in mind throughout this discussion are that (1) the heart can only pump what it gets; and (2) a healthy heart pumps all of the blood returned to it. The SA node may generate a heartbeat and cause the ventricles to contract; however, these chambers must be properly filled with blood in order for this activity to be effective. On the other hand, the volume of blood that returns to the heart per minute may vary considerably. The heart has an intrinsic ability to alter its strength of contraction in order to accommodate these changes in volume.

Diastole is the period in the cardiac cycle in which relaxation of the myocardium and ventricular filling take place. In an individual with a resting heart rate of 75 beats per minute, the length of the cardiac cycle is 0.8 sec and the length of ventricular diastole is 0.5 sec. As mentioned in the previous chapter, the end-diastolic volume is approximately 130 ml and the resulting stroke volume is about 70 ml. Consider a case in which the heart rate is increased. Given that cardiac output is determined by heart rate multiplied by stroke volume, an increase in either of these variables should result in an increase in cardiac output.

In general, this is quite true; however, the effect of increased heart rate on cardiac output is limited by its effect on the length of diastole. As heart rate increases, the length of the cardiac cycle and therefore the length of diastole or the time for filling will decrease. At very high heart rates, this may result in a decrease in ventricular filling or end-diastolic volume; a decrease in stroke volume; and a decrease in cardiac output. Once again, "the heart can only pump what it gets." If time for filling is inadequate, then despite an increase in heart rate, cardiac output will actually decrease. This explains why the maximal heart rate during exercise is about 195 beats per minute in all individuals. Beyond this rate, the ventricles are unable to fill with blood properly and the positive effect of increased heart rate on cardiac output is lost.

Venous return is defined as the volume of blood returned to the right atrium per minute. Assuming a constant heart rate and therefore a constant length of diastole, an increase in venous return, or the rate of blood flow into the heart, will increase ventricular filling, end-diastolic volume, stroke volume, and cardiac output. Ventricular blood volume prior to contraction is also referred to as preload. Once again, "a healthy heart pumps all of the blood returned to it." In fact, cardiac output is equal to venous return. The heart has an inherent, self-regulating mechanism by which it can alter its force of contraction based upon the volume of blood that flows into it. This intrinsic mechanism, the Frank-Starling law of the heart, states that when ventricular filling is increased, this increased volume of blood stretches the walls of these chambers and, as a result, the ventricles contract more forcefully. The stronger contraction results in a larger stroke volume.

This concept is illustrated by the cardiac function curve (see Figure 14.2). As end-diastolic volume increases, stroke volume and therefore cardiac output increase. This phenomenon is based on the length-tension relationship of cardiac muscle. Recall in the discussion of skeletal muscle in Chapter 11 that the resting length of the sarcomere determines the amount of tension generated by the muscle upon stimulation. Due to their attachments to the bones, the resting lengths of skeletal muscles do not vary greatly. Therefore, the sarcomeres are normally at their optimal length of 2.2 mm, resulting in maximal tension development. At this point, the overlap of the actin and myosin filaments in the sarcomere is such that the greatest amount of cross-bridge cycling to generate tension takes place. The myocardium of the heart, however, is not limited by attachment to any bones. Therefore, the resting length of the sarcomeres of these muscle cells may vary substantially due to changes in ventricular filling.

. Hypereffective heart

Normal heart m

Hypoeffective heart

End-diastolic volume (ml)

Figure 14.2 Cardiac function curve. This curve illustrates the stroke volume pumped by the heart for a given end-diastolic volume within the ventricle. As ventricular filling (end-diastolic volume) increases, stroke volume increases. Factors causing a positive inotropic effect (increased contractility) result in greater stroke volume for a given amount of filling compared to the normal heart. This "hypereffective" heart is illustrated by the short dashed line shifted to the left of that of the normal heart. Factors causing a negative inotropic effect (decreased contractility) result in reduced stroke volume for a given amount of filling. This "hypoeffective" heart is illustrated by the long dashed line shifted to the right of that of the normal heart.

Interestingly, at a normal resting end-diastolic volume of 130 ml, the amount of ventricular filling and resting cardiac muscle fiber length is less than the optimal length. Therefore, as filling increases, muscle fibers and their component sarcomeres are stretched and move closer to the optimal length for crossbridge cycling and tension development. This results in a stronger ventricular contraction and an increase in stroke volume. In other words, a healthy heart operates on the ascending portion of the cardiac function curve, so an increase in preload results in an increase in stroke volume.

Pharmacy application: diuretics and cardiac output

Diuretics are a group of therapeutic agents designed to reduce the volume of body fluids. Their mechanism of action is at the level of the kidney and involves an increase in the excretion of Na+ and Cl- ions and, consequently, an increase in urine production. As discussed in Chapter 2, sodium is the predominant extracellular cation and, due to its osmotic effects, a primary determinant of extracellular fluid volume. Therefore, if more sodium is excreted in the urine, then more water is also lost, thus reducing the volume of extracellular fluids including the plasma.

As plasma volume decreases, less blood is available for ventricular filling.

It is this reduction in preload that, in some cases, is beneficial to patients experiencing heart failure or hypertension. Unlike a healthy heart, a failing heart is unable to pump all of the blood returned to it. Instead, the blood dams up and overfills the chambers of the heart. This results in congestion and increased pressures in the heart and venous system and the formation of peripheral edema. Because the failing heart is operating on the flat portion of a depressed cardiac function curve (see Figure 14.2), treatment with diuretics will relieve the congestion and edema, but have little effect on stroke volume and cardiac output.

Hypertension (blood pressure >140/90 mmHg) may be caused by an elevation in cardiac output or excessive vasoconstriction. Diuretics are used in these patients to reduce cardiac output. Assume that the hearts of these individuals are operating on the ascending portion of the cardiac function curve. As the plasma volume is reduced in response to treatment with diuretic drugs, venous return and preload are reduced, as are ventricular filling and stroke volume, and cardiac output, thus bringing blood pressure back within the normal range.

Stimulation of the ventricular myocardium by the sympathetic system will also increase stroke volume by increasing contractility of the muscle. At any given end-diastolic volume, norepinephrine released from the sympathetic nerves to the heart will cause a more forceful contraction resulting in the ejection of more blood from the ventricles or an increase in stroke volume and in cardiac output (see Figure 14.2). In other words, the cardiac function curve shifts to the left. Epinephrine released from the adrenal medulla has the same effect on contractility as direct sympathetic stimulation. The mechanism involves the stimulation of b-adrenergic receptors and the subsequent increase in permeability to calcium. An increase in intracellular calcium results in increased crossbridge cycling and greater tension development. Sympathetic stimulation, circulating catecholamines, or any other factor that increases contractility has a positive inotropic effect on the heart. Therapeutic agents, such as b-adrenergic receptor blockers and calcium channel blockers that inhibit calcium influx and therefore contractility, have a negative inotropic effect.

The contractility of the myocardium determines the ejection fraction of the heart, which is the ratio of the volume of blood ejected from the left ventricle per beat (stroke volume) to the volume of blood in the left ventricle at the end of diastole (end-diastolic volume):

Ejection fraction = SV n EDV

Under normal resting conditions in which the end-diastolic volume is 120 to 130 ml and the stroke volume is 70 ml/beat, the ejection fraction is 55 to 60%:

Ejection fraction = 70 ml/beat n 120ml = 58%

During exercise when sympathetic stimulation to the heart is increased, the ejection fraction may increase to more than 80% resulting in greater stroke volume and cardiac output.

Another factor determining cardiac performance is afterload, or the pressure in the artery leading from the ventricle. When the ventricle contracts, it must develop a pressure greater than that in the associated artery in order to push open the semilunar valve and eject the blood (see Chapter 13). Typically, diastolic blood pressure in the aorta is 80 mmHg; therefore, the left ventricle must develop a pressure slightly greater than 80 mmHg to open the aortic valve and eject the stroke volume. A dynamic exercise such as running may cause only a small increase in diastolic pressure (up to 90 mmHg), although a resistance exercise such as weight lifting, which has a much greater impact on blood pressure and diastolic pressure, may be as high as 150 to 160 mmHg.

A healthy heart can easily contract vigorously enough to overcome any increases in afterload associated with exercise or other types of physical exertion. In contrast, however, a diseased heart or one weakened by advanced age may not be able to generate enough force to overcome a significantly elevated afterload effectively. In this case, stroke volume and cardiac output would be reduced. In addition, a sustained or chronic increase in afterload, as observed in patients with hypertension, will also have a detrimental effect on cardiac workload. Initially, the left ventricle will hypertrophy and chamber walls will become thicker and stronger to compensate for this excess workload. However, eventually the balance between the oxygen supply and oxygen demand of the heart is disrupted, leading to decreased stroke volume, decreased cardiac output, and heart failure.

Changes in heart rate also affect the contractility of the heart. As heart rate increases, so does ventricular contractility. The mechanism of this effect involves the gradual increase of intracellular calcium. When the electrical impulse stimulates the myocardial cell, permeability to calcium is increased and calcium enters the cell, allowing it to contract. Between beats, the calcium is removed from the intracellular fluid and the muscle relaxes. When heart rate is increased, periods of calcium influx occur more frequently and time for calcium removal is reduced. The net effect is an increase in intracellular calcium, an increased number of crossbridges' cycling, and an increase in tension development.

Pharmacy application: cardiac glycosides and cardiac output

A patient is considered to be in heart failure when cardiac output is insufficient to meet the metabolic demands of his body. The most effective method to improve cardiac output is to enhance myocardial contractility, which will increase stroke volume. Because of their positive inotropic effect, the cardiac glycosides, including digoxin, have been used for many years to treat heart failure. Digoxin binds to and inhibits the Na+-K+ ATPase in the myocardial cell membrane, ultimately leading to an increase in the intracellular concentration of calcium. As described previously, any increase in calcium will increase my-ocardial contractility, stroke volume, and cardiac output.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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