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Young DB. Control of Cardiac Output. San Rafael (CA): Morgan & Claypool Life Sciences; 2010.

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Control of Cardiac Output.

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Chapter 3Cardiac Function

The heart is a powerful, complex organ that has fascinated scholars, poets, and physicians for centuries. It provides the energy for the flow of life-giving blood through the circulatory system, and its strong, rhythmic beating is the very symbol of life. Cardiac physiology has been studied intensively, yielding an advanced understanding of the heart’s intrinsic function. But for this presentation, the mechanisms of the heart’s inner workings are not the subject of greatest interest. Here, the object is to provide an analysis of regulation of cardiac output, and to that end, what is required is knowledge concerning how the heart functions as a component of the circulatory system. The healthy heart can increase its output approximately 3- to 4-fold, but only if blood flows into the right atrium at three or four times the normal rate. If the heart pumps blood into the aorta or pulmonary artery faster than it enters the atria, pressure in the atria will fall, the veins will begin to collapse, resistance to venous return will increase, and flow into the atria will fall, thereby limiting cardiac output to the rate at which blood returns to the heart. Regardless of how forcefully the myocardium contracts, the flow of blood from the heart cannot exceed the rate of venous return for longer than a few seconds. In conditions of health, the function of the heart alone cannot determine cardiac output, for the heart is only one component of a complex system. Therefore, the vitally important and fascinating subjects concerning the physiology of the myocardium will not be included here; rather, the focus will be on the characteristics of the heart as a pump within the system that regulates cardiac output.

3.1. Cardiac Output Curves

One of the first observations made by pioneering cardiac investigators was that the function of the heart was strongly influenced by the level of atrial pressure, the force of contraction increasing dramatically as atrial pressure increased. Therefore, cardiac performance has been expressed as various functions of right or left atrial pressure for nearly a century, beginning with Patterson and Starling [14] and Wiggers [15]. Atrial pressure may be plotted as the independent variable with various measures of cardiac function plotted as the dependent variable. Four types of function curves have been used most frequently: cardiac output plotted versus mean right atrial pressure; pressure output of each ventricle plotted versus ventricular end diastolic volume; ventricular work output plotted versus mean atrial pressure; and ventricular power output plotted versus mean atrial pressure. Each of these conveys valuable amounts of information of different types. However, the function curve relating cardiac output to mean right atrial pressure is most useful for analysis of the heart’s function in the circulatory system in which venous return and the cardiac pump work together in series.

For nearly all circumstances that will be considered here, the functions of the right and left ventricles can be considered as one unit. The main exceptions are conditions in which the right or left ventricles undergo pathological changes separately or when other factors create imbalance between the pumping abilities of the two ventricles. But in other conditions, the heart can be considered accurately as a single unit in which cardiac output is related to right atrial pressure.

Cardiac function curves can be derived from experiments in rats or larger experimental animals in which right atrial pressure is changed in a controlled manner while cardiac output is measured continuously. To obtain data from closed-chest preparations, right atrial pressure may be controlled by rapidly infusing or withdrawing blood through a large bore catheter placed in the right atrium from the external jugular vein. Ideally, the data for the complete curve should be obtained within 45–60 s, before the conditions of the heart and circulatory system change in response to experimental manipulation. If the experiment is conducted properly, data points for a function curve similar to the curve in Figure 3.1 will be obtained. At the normal right atrial pressure (0 mm Hg), cardiac output will be at its normal value, approximately 5 L/min for a normal size healthy human. As right atrial pressure is reduced below 0 mm Hg, cardiac output decreases until, in the normal, closed-chest situation, at right atrial pressure of –2 to –3 mm Hg, cardiac output reaches 0. The progressive reduction in output is due to the Starling effect (reduction in length of stretch of cardiac muscle fibers, discussed in the following paragraph). Increasing right atrial pressure above normal is associated with very steep increases in cardiac output, until at a right atrial pressure of 3–4 mm Hg, cardiac output increases to its maximum, approximately three to four times the normal level. Further increases in right atrial pressure are not associated with additional increases in cardiac output, a plateau level being reached at right atrial pressure of 3–4 mm Hg.

FIGURE 3.1. The cardiac function curve, with cardiac output values scaled to normal human levels.

FIGURE 3.1

The cardiac function curve, with cardiac output values scaled to normal human levels.

Most noteworthy is the large increase in cardiac output with each small incremental increase in the right atrial pressure in the range between –1 and 1 mm Hg. This reflects the heart’s capacity to respond robustly and rapidly to even small changes in atrial pressure within the normal range of right atrial pressure. This exceptional capability is due to the effect of stretch on the cardiac muscle fibers. With increasing ventricular end diastolic pressure, ventricular volume increases, lengthening the cardiac muscle fibers. Consequently, the force of contraction of the fibers increases so that the pumping ability of the ventricle is markedly augmented. The effect was described by Starling and associates nearly a century ago and is referred to as Starling’s law of the heart [14, 16]. This intrinsic cardiac function enables the heart to double its output within a single contraction when end diastolic pressure is increased from normal to 1 or 2 mm Hg. However, the heart reaches its limit of force generation when the muscle fibers are stretched to their greatest effective length. The mean ventricular end diastolic pressure at which the cardiac output reaches a plateau is the filling pressure that produces the greatest force generation from the ventricle.

If the condition of the heart deteriorates during the data collection period, the resulting function curve may have a “hump” and a descending limb at high levels of right atrial pressure. Prolonging the experimental procedure to obtain data for longer than several minutes may fatigue or damage the heart, especially at high levels of right atrial pressure. Under such conditions, the data obtained may not yield a curve with a stable plateau. Instead, it may have a hump and a descending leg at higher levels of right atrial pressure, as in the one plotted in dashes in Figure 3.2.

FIGURE 3.2. A cardiac function curve with a descending leg in the upper range of atrial pressure.

FIGURE 3.2

A cardiac function curve with a descending leg in the upper range of atrial pressure. The descending portion may be due to deterioration of the myocardium due to fatigue or injury associated with excessive length of time required for data collection. (more...)

In reality, the curve represents a compilation of data from a series of time-dependent function curves, each reflecting the progressive weakening of the heart during the course of the study. As the experiment progresses to higher levels of right atrial pressure, the myocardium weakens so that the data collected were not from the heart in its initial condition. Consequently, at each level of deterioration, the function curve is shifted downward. In reality, the data from an excessively lengthy study could be described by a series of time-dependent function curves such as those presented in Figure 3.3.

FIGURE 3.3. A series of function curves obtained over an extended period illustrating how a descending portion could be erroneously obtained.

FIGURE 3.3

A series of function curves obtained over an extended period illustrating how a descending portion could be erroneously obtained.

If an assumption is made incorrectly that the heart’s function remains unchanged during the time the right atrial pressure is raised, the data collected over the 4-min period would be plotted as a series of data for one curve, with a descending leg at higher levels of right atrial pressure. Such curves have appeared in the literature as “classic” cardiac function curves, although in reality, they are data points obtained from a series of time-dependent curves from the progressively weakening heart. Within the normal range of right atrial pressure, the accurate cardiac function curve has a stable plateau [1719].

3.2. Factors That Alter Cardiac Output By Changing The Effectiveness Of The Pumping Ability Of The Heart

Systemic resistance and arterial pressure affect the cardiac function curve. Data for cardiac function curves may be obtained from experiments in which either the systemic resistance or the systemic arterial pressure is controlled. If the resistive load is held constant, arterial pressure will increase progressively as cardiac output increases, and consequently, the effectiveness of the pumping ability of the left ventricle will be limited as the outflow pressure increases to higher levels, as illustrated in Figure 3.4.

FIGURE 3.4. Cardiac function curves obtained at different fixed levels of arterial resistance.

FIGURE 3.4

Cardiac function curves obtained at different fixed levels of arterial resistance. Reducing resistance to 75% of normal results in only a slight increase in the slope and plateau, although increasing resistance to 150% of normal significantly limits output (more...)

If the load is reduced, cardiac output will be affected only slightly. This is because the output of the right ventricle is near maximal even under conditions of normal arterial resistance, so that reduction in arterial load will not result in a significant increase in output of the right ventricle or the left ventricle.

But if the data are obtained from a constant pressure study rather than one in which resistive load is held constant, the pumping ability of the heart will not be constrained by continually increasing arterial pressure as cardiac output rises. Figure 3.5 presents the expected shapes for function curves when resistive load is held constant and when pressure load is maintained at a fixed, normal level.

FIGURE 3.5. Differing effects of a fixed resistive load and a fixed pressure load on the cardiac function curve.

FIGURE 3.5

Differing effects of a fixed resistive load and a fixed pressure load on the cardiac function curve.

Most data for cardiac output function curves are obtained from intact, closed-chest animal preparations in which neither arterial pressure nor resistive load can be controlled. But in a properly conducted study, during which the data are rapidly collected, resistance changes very little and may even decrease as the increasing arterial pressure stretches the arteries slightly. These studies cannot be termed constant resistance but can be called “normal resistance” function studies. Most of the cardiac output function curves in this presentation were derived from data obtained with normal resistive load.

Sagawa and associates performed an in-depth analysis of the relationships between left atrial pressure and cardiac output [21] and between right atrial pressure and cardiac output [22], in both cases with arterial pressure controlled in steps over a range of 0–250 mm Hg. Their data are plotted in three dimensions in Figure 3.6.

FIGURE 3.6. The three-dimensional interrelationship between atrial pressure, arterial pressure, and cardiac output: (A) left atrial pressure–arterial pressure cardiac output function; (B) right atrial pressure–arterial pressure cardiac out function.

FIGURE 3.6

The three-dimensional interrelationship between atrial pressure, arterial pressure, and cardiac output: (A) left atrial pressure–arterial pressure cardiac output function; (B) right atrial pressure–arterial pressure cardiac out function. (more...)

The output of the left ventricle increases progressively as left atrial pressure increases to as high as 20 mm Hg (3.6 A), especially when mean arterial pressure is controlled at levels below 100 mm Hg. Little evidence of a stable plateau value appears until arterial pressure is maintained near 200 mm Hg. In contrast, the output of the total heart (3.6 B) fails to increase as right atrial pressure is raised above 8 mm Hg (open-chest preparation) even when arterial pressure is maintained at 100 mm Hg. Taken together, these observations imply that the pumping ability of the heart is limited by the ability of the right ventricle to increase its output to levels greater than those attained at relatively low right atrial pressure and that cardiac output is relatively insensitive to the effects changes in mean arterial pressure below 150 mm Hg.

Increasing heart rate up to the optimal level increases the slope and plateau value of the cardiac function curve. Changing only the heart rate affects the pumping ability of the heart, even when all other factors remain constant. With increases in rate, the slope increases as well as the plateau until the rate is approximately 80–100% greater than normal (Figure 3.7). At some rate less than the maximal heart rate, the greatest increase in pumping ability is achieved; above this optimal rate, cardiac output declines progressively. The decease in function at supraoptimal heart rate is due to inadequate time for filling of the heart during diastole. Possibly, the pressure gradient for flow into the ventricles may influence the optimal heart rate, with higher levels of pressure gradient being associated with higher optimal heart rates.

FIGURE 3.7. Cardiac function curves obtained at different fixed heart rates.

FIGURE 3.7

Cardiac function curves obtained at different fixed heart rates.

The autonomic nervous system affects both heart rate and strength of contraction. Cardiac output must be able to respond quickly to the needs of the body in response to a variety of normal changes in activity or environment. The autonomic nervous system can produce rapid changes in cardiac function, with the sympathetic system increasing and the parasympathetic decreasing the pumping ability of the heart.

The sympathetic system acts via the adrenergic cardiac nerves that innervate the atria and ventricles and release norepinepherine, and by secretion of epinephrine and norepinepherine from the adrenal medulla, reaching the heart through the circulation. In both cases, the effect on the heart is an increase in heart rate and in cardiac contractility, shifting the cardiac function curve to the left due to the effect on the slope of the curve, and increasing the plateau value. Interrupting sympathetic tone to a resting animal will reduce heart rate by only a few beats per minute, demonstrating that, in the normal resting condition, sympathetic stimulation of the heart is minimal. But if the sympathetic cardiac nerves are maximally stimulated while vagal input is blocked, heart rate can more than double. The upper curve in Figure 3.8 illustrates the shift in the function curve from its normal position to the maximal sympathetic stimulated state. With maximal stimulation, the plateau is increased to approximately 70% above normal [18]. If, in a normal subject or animal, all sympathetic nervous system activity were blocked, the cardiac function curve would be shifted downward and to the right due to withdrawal of the normal, tonic sympathetic stimulation.

FIGURE 3.8. Effects of autonomic nervous system input to the heart on the cardiac function curve. From reference [18].

FIGURE 3.8

Effects of autonomic nervous system input to the heart on the cardiac function curve. From reference [18].

The data used for Figure 3.8 were obtained from studies in which right atrial pressure was controlled as described previously to obtain complete function curve data. However, in an intact animal preparation or in a healthy human, if sympathetic stimulation to only the heart increases strongly, cardiac output may increase slightly or may remain unchanged while right atrial pressure will decrease. This combination may appear paradoxical, but it can be explained by the adrenergic augmentation of myocardial contractility increasing the slope of the function curve, shifting it to the left; however, because venous return does not rise, cardiac output will remain nearly unchanged. With adrenergic stimulation, the heart is operating on a shifted curve, one at which the nearly unchanged cardiac output is achieved at a reduced level of right atrial pressure. The curves describing the two conditions and the change in right atrial pressure at a constant cardiac output are illustrated in Figure 3.9.

FIGURE 3.9. Effect of maximal cardiac sympathetic stimulation on the cardiac function curve in an intact preparation.

FIGURE 3.9

Effect of maximal cardiac sympathetic stimulation on the cardiac function curve in an intact preparation.

Parasympathetic input to the heart is mediated by acetylcholine released from the branches of the vagus nerve that innervate the sinoatrial node in the right atrium. Some cholinergic fibers originating from the vagus are also distributed to the ventricles. Increases in parasympathetic activity decrease heart rate from the normal level and can actually stop the heart for a few seconds if stimulation is maximal, although the heart escapes and rate will stabilize at approximately one-third the normal rate. Totally blocking vagal input while an animal is in a resting state will increase heart rate by approximately 35%. Parasympathetic activity has some negative effect on ventricular contractility as well [23, 24], although the effects are not nearly as significant as the stimulatory effects of sympathetic stimulation. Figure 3.8 illustrates the shift in the cardiac function curve resulting from maximal parasympathetic activity after escape (blue curve).

Heart rate is determined by a complex interaction between the effects of sympathetic and parasympathetic systems. Figure 3.10, derived from data of Levy and Zeiske [26], illustrates the heart rates resulting from combined frequencies of stimulation of the parasympathetic and sympathetic nerves innervating the heart. The resulting three-dimensional surface reveals the nature of the complexity. Notice that, as vagal stimulation increases, the effect of sympathetic stimulation on heart rate decreases, so that at the highest vagal stimulation (8 Hz), the heart rate response to sympathetic stimulation is minimal, even at the highest rate of sympathetic stimulation. At lower vagal frequencies, the response to elevated sympathetic discharge rates is several times greater. A similar relationship exists between the changes in heart rate in response to vagal stimulation at fixed levels of sympathetic tone, although the effect of parasympathetic innervation is not attenuated to the extent observed with the sympathetic response at high levels of vagal input.

FIGURE 3.10. Three-dimensional interrelationships between sympathetic and parasympathetic stimulation of the heart on cardiac function.

FIGURE 3.10

Three-dimensional interrelationships between sympathetic and parasympathetic stimulation of the heart on cardiac function. Reproduced with permission of Elsevier from reference [25], derived from data from reference [26].

Myocardial disease or damage shifts the cardiac function curve to the right and downward. The effects of coronary vascular disease on cardiac function are complex, and it is difficult to make generalizations about the effects, especially so since very little applicable data exist. However, several experimental models of coronary artery constriction have been studied [2730]. Curves derived from such studies are presented in Figure 3.11, illustrating that, with ischemic or hypoxic impairment of myocardial metabolism, both the slope and plateau of the cardiac function curve are depressed. Data describing the function curves’ characteristic in forms of chronic heart failure, such as hypertrophy or dilated cardiomyopathy, are not available, although in all forms of cardiac failure, one may expect the cardiac function curve to be depressed and shifted to the left.

FIGURE 3.11. Impact of differing degrees of coronary artery occlusion on the cardiac function curve.

FIGURE 3.11

Impact of differing degrees of coronary artery occlusion on the cardiac function curve.

3.3. Factors That Alter Cardiac Output By Changing Extracardiac Pressure

Reduction in the atrial transmural pressure gradient shifts the cardiac function curve to the left. If the chest is opened, intrathorasic pressure increases from its mean value of approximately –4 mm Hg to atmospheric pressure, and consequently, the pressure gradient across the wall of the right atrium decreases by 4 mm Hg. In this condition, the cardiac function curve is shifted in a parallel manner to the right by 4 mm Hg; at all points on the curve, right atrial pressure must be 4 mm Hg higher to achieve a comparable level of output on the normal curve. Breathing against positive pressure shifts the curve to the right as well, while a shift in the opposite direction results from breathing again negative pressure. The plateau value of cardiac output is not affected by changes in the pressure gradient across the atrial wall.

Cardiac tamponade reduces the slope of the cardiac function curve. Cardiac tamponade is a condition caused by accumulation of fluid in the pericardium due to infection, trauma, or hemorrhage. Because the pericardium has low compliance, the increase in volume caused by the fluid increases intrapericardial pressure and reduces the atrial transmural pressure gradient. As a result, the cardiac function curve is shifted to the right, indicating that a higher level of atrial pressure must be reached in order attain a given level of cardiac output on the normal function curve. The situation is somewhat similar to the effect of increased intrapleural pressure or positive pressure breathing, except that in the case of cardiac tamponade, the pressure outside the atrium is not constant; rather, due to the low pericardial compliance, the pericardial pressure increases as cardiac volume and pericardial fluid volume increase. Cardiac volume increases as atrial pressure increases; therefore, as atrial pressure rises, pericardial pressure increases, limiting the rise in atrial transmural pressure gradient. Cardiac function curves produced in various degrees of tamponade are presented in Figure 3.12. The severity of tamponade is related to the volume of fluid and the pressure within the pericardium. Notice that the slope of the curves is reduced progressively as atrial pressure increased due to the progressive expansion of the heart. Furthermore, the plateau is reduced and may not be achieved at all at physiological levels of atrial pressure.

FIGURE 3.12. Effects of cardiac tamponade on the cardiac function curve.

FIGURE 3.12

Effects of cardiac tamponade on the cardiac function curve.

3.4. Summary

The pumping of the heart working as an integral part of the cardiovascular system can be described quantitatively by function curves relating cardiac output as the dependent variable to right atrial pressure as the independent variable. Regardless of its condition or the factors affecting it, the heart’s function in the system is accurately reflected by its cardiac function curve. Furthermore, cardiac output can be predicted from right atrial pressure if the cardiac function curve is known.

Cardiac function curves can be altered by two types of factors: changes in the effectiveness of the pumping ability of the heart and changes in extracardiac pressure. The family of cardiac function curves resulting from the effects of changes in strength and effectiveness of pumping is shown in Figure 3.13, and the family of curves resulting from changes in extracardiac pressure is presented in Figure 3.14.

FIGURE 3.13. Effects of intrinsic changes in pumping ability of the heart on the cardiac function curve.

FIGURE 3.13

Effects of intrinsic changes in pumping ability of the heart on the cardiac function curve.

FIGURE 3.14. Effects of pressure outside the heart on the cardiac function curve are illustrated here.

FIGURE 3.14

Effects of pressure outside the heart on the cardiac function curve are illustrated here.

Copyright © 2010 by Morgan & Claypool Life Sciences.
Bookshelf ID: NBK54477

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