Chapter 10_ Cardiovascular Responses to Physiological Stresses | Cardiovascular Physiology: Mosby Physiology Monograph Series, 9e (Mosbys Physiology Monograph)

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Objectives

The student understands the general mechanisms involved in the cardiovascular responses to any given normal homeostatic disturbance on the intact cardiovascular system and can predict the resulting alterations in all important cardiovascular variables:

Identifies the primary disturbances that the situation places on the cardiovascular system.
Lists how the primary disturbances change the influence on the medullary cardiovascular centers from (1) arterial baroreceptors and (2) other sources.
States what immediate reflex compensatory changes will occur in sympathetic and parasympathetic nerve activities as a result of the altered influences on the medullary cardiovascular centers.
Indicates what immediate reflex compensatory changes will occur in basic cardiovascular variables such as heart rate, cardiac contractility, stroke volume, arteriolar tone, venous tone, peripheral venous pressure, central venous pressure, total peripheral resistance, resistance in any major organ, and blood flow through any major organ.
Predicts what the net effect of the primary disturbance and reflex compensatory influences on the cardiovascular variables listed in the preceeding objective will be on mean arterial pressure.
States whether mean arterial pressure and sympathetic nerve activity will settle above or below their normal values.
Predicts whether and states how cutaneous blood flow will be altered by temperature regulation reflexes.
Indicates whether and how transcapillary fluid movements will be involved in the overall cardiovascular response to a given primary disturbance.
Indicates whether, why, how, and with what time course renal adjustments of fluid balance will participate in the response.
Predicts how each of the basic cardiovascular variables will be influenced by long-term adjustments in blood volume.

The student understands how respiratory activities influence the cardiovascular system:

Describes how the "respiratory pump" promotes venous return.
Identifies the primary disturbances on cardiovascular variables associated with normal respiratory activity.
Describes the reflex compensatory responses to respiratory activity.
Defines the causes of "normal sinus arrhythmia."
Lists the cardiovascular consequences of the Valsalva maneuver and of positive pressure artificial ventilation.

The student understands the specific processes associated with the homeostatic adjustments to the effects of gravity:

States how gravity influences arterial, venous, and capillary pressures at any height above or below the heart in a standing individual.
Describes and explains the changes in central venous pressure and the changes in transcapillary fluid balance and venous volume in the lower extremities caused by standing upright.
Describes the operation of the "skeletal muscle pump" and explains how it simultaneously promotes venous return and decreases capillary hydrostatic pressure in the muscle vascular beds.
Identifies the primary disturbances and compensatory responses evoked by acute changes in body position.
Describes the chronic effects of long-term bed rest on cardiovascular variables.

The student understands the specific processes associated with the homeostatic adjustments to exercise:

Identifies the primary disturbances and compensatory responses evoked by acute episodes of dynamic exercise.
Describes the conflict between pressure reflexes and temperature reflexes on cutaneous blood flow.
Indicates how the "skeletal muscle pump" and the "respiratory pump" contribute to cardiovascular adjustments during exercise.
Compares the cardiovascular responses to static exercise with those to dynamic exercise.
Lists the effects of chronic exercise and physical conditioning on cardiovascular variables.

The student understands that gender may influence the cardiovascular system:

Describes gender-dependent differences in cardiovascular variables.

The student understands the cardiovascular alterations that accompany birth, growth, and aging:

Identifies the pathway of blood flow through the fetal heart and describes the changes that occur at birth.
Indicates the normal changes that occur in cardiovascular variables during childhood.
Identifies age-dependent changes that occur in cardiovascular variables such as cardiac index, arterial pressure, and cardiac workload.
Describes age-dependent changes in the arterial baroreceptor reflex.
Distinguishes between age- and disease-dependent alterations that occur in cardiovascular function of the aged.

Cardiovascular Responses to Physiological Stresses: Introduction

This chapter as well as Chapter 11 will show how the basic principles of cardiovascular physiology which have been discussed apply to the intact cardiovascular system. A variety of situations that tend to disturb homeostasis will be presented. The key to understanding the cardiovascular adjustments in each situation is to recall that the arterial baroreceptor reflex and renal fluid balance mechanisms always act to blunt changes in arterial pressure. The overall result is that adequate blood flow to the brain and the heart muscle is maintained in any circumstance.

The cardiovascular alterations in each of the following examples are produced by the combined effects of (1) the primary, direct influences of the disturbance on the cardiovascular variables and (2) the reflex compensatory adjustments that are triggered by the primary disturbances. The general pattern of reflex adjustment is similar in all situations. Rather than trying to memorize the cardiovascular alterations that accompany each situation, the student should strive to understand each response in terms of the primary disturbances and reflex compensatory reactions involved. To aid in this process, a list of key cardiovascular variables and their determinants may be found in Appendix C.

A list of important study questions is supplied for Chapters 10 and 11. These questions are intended to reinforce the student's understanding of complex cardiovascular responses and provide a review of basic cardiovascular principles.

Effect of Respiratory Activity

The physical processes associated with inhaling air into and exhaling air out of the lungs can have major effects on venous return and cardiac output. During a normal inspiration, intrathoracic pressure falls by about 7 mmHg as the diaphragm contracts and the chest wall expands. It rises again by an equal amount during expiration. These periodic pressure fluctuations not only promote air movement into and out of the lungs but also are transmitted through the thin walls of the great veins in the thorax to influence venous return to the heart from the periphery. Because of the venous valves, venous return is increased more by inspiration than it is decreased by expiration. The net effect is that venous return from the periphery is generally facilitated by the periodic fluctuations in central venous pressure caused by respiration. This phenomenon is often referred to as the "respiratory pump."

Because of these changes in venous return, normal breathing is associated with transient cyclical changes in cardiac output and arterial pressure. Heart rate in normal individuals also fluctuates in synchrony with the respiratory rate. This is referred to as "normal sinus arrhythmia." Some of the major primary disturbances and compensatory responses involved in the cardiovascular effects of respiration are illustrated in Figure 10 1, although the complete picture is much more complex than shown. Filling of the right side of the heart is transiently increased during inspiration and, by Starling's law, stroke volume and thus cardiac output are transiently increased. Since changes in output of the right side of the heart induce changes in output of the left side of the heart, the net effect of inspiration will be a transient increase in stroke volume and cardiac output from the left ventricle. This will lead to a transient increase in arterial pressure and a transient increase in firing of the arterial baroreceptors. In addition, because of the inspiration-induced decrease in intrathoracic pressure, the cardiopulmonary baroreceptors in the vascular and cardiac walls will be stretched and will increase their firing rate. These baroreceptor inputs will act on the medullary cardiovascular centers to produce reflex adjustments to lower arterial pressure: that is, increase cardiac parasympathetic nerve activity and decrease sympathetic nerve activity. Under normal resting conditions, the cyclic change in heart rate is the most apparent cardiovascular response to respiration.¹

There are a number of instances when cardiovascular effects of respiratory efforts are extremely important. In exercise, for example, a deep and rapid breathing rate contributes significantly to the venous return. Yawning is a complex event that includes a significant transient decrease in intrathoracic pressure that is effective in increasing venous return (especially when combined with stretching). In contrast, coughing is associated with an increase in intrathoracic pressure and, if occurring as a prolonged "fit," can lead to such severe reductions in cardiac output as to cause fainting.

The cardiovascular consequences of changes in intrathoracic pressure are also important during the Valsalva maneuver, which is a forced expiration against a closed glottis. This maneuver is normally performed by individuals during defecation ("straining at stool"), or when attempting to lift a heavy object. (Similar conditions exist when forced expirations are made against a high output resistance, such as when blowing up one of those nasty little party balloons.) There are several phases in this cardiovascular reaction. At the initiation of the Valsalva maneuver, arterial pressure is abruptly elevated for several beats due to the intrathoracic pressure transmitted to the thoracic aorta. The sustained elevation in intrathoracic pressure leads to a fall in venous return and a fall in blood pressure, which evokes a compensatory reflex increase in heart rate and peripheral vasoconstriction. (During this period, the red face and distended peripheral veins are indicative of high peripheral venous pressures.) At the cessation of the maneuver, there is an abrupt fall in pressure for a couple of beats due to the reduction of intrathoracic pressure. Venous blood then moves rapidly into the central venous pool; stroke volume, cardiac output, and arterial pressure increase rapidly; and a reflex bradycardia occurs. The combination of an episode of high peripheral venous pressure followed by an episode of high arterial pressure and pulse pressure is particularly dangerous for people who are candidates for cerebral vascular accidents (strokes) because this combination may rupture a vessel.

Artificial changes in intrathoracic pressure evoked during forced respiration with a positive pressure ventilator have significant adverse cardiovascular consequences. When the lungs are inflated artificially, intrathoracic pressure goes up (rather than down, as occurs during normal inspiration). Thus, instead of the normal respiratory pump increasing venous return during inspiration, the positive pressure ventilator decreases venous return during lung inflation. In addition, the increase in intrathoracic pressure tends to compress the pulmonary microcirculation and this increases right ventricular afterload.

¹ Although the respiratory effects of right heart filling are emphasized in Figure 10 1, respiration also directly affects left heart filling. However, the events are somewhat different because both the left atria and the whole of the pulmonary vascular system are affected by changes in intrathoracic pressure. There are also some time delays between changes in right heart filling and left ventricular stroke volume that are ignored in Figure 10 1. The specific phase relationships between the respiratory cycle and the cardiovascular effects are influenced by respiratory rate and depth as well as the current average heart rate.

Effect of Gravity

Responses to Changes in Body Position

Significant cardiovascular readjustments accompany changes in body position because gravity has an effect on pressures within the cardiovascular system. In the preceding chapters, the influence of gravity was ignored and pressure differences between various points in the systemic circulation were related only to flow and vascular resistance (P = R). As shown in Figure 10 2, this is approximately true only for a recumbent individual. In a standing individual, additional cardiovascular pressure differences exist between the heart and regions that are not at heart level. This is most important in the lower legs and feet of a standing individual. As indicated in Figure 10 2B, all intravascular pressures in the feet may be increased by 90 mmHg simply from the weight of the blood in the arteries and veins leading to and from the feet. Note by comparing Figure 10 2A and B that standing upright does not in itself change the flow through the lower extremities, since gravity has the same effect on arterial and venous pressures and thus does not change the arteriovenous pressure difference at any one height level. There are, however, two major direct effects of the increased pressure in the lower extremities that are shown in Figure 10 2B: (1) the increase in venous transmural pressure distends the compliant peripheral veins and greatly increases peripheral venous volume by as much as 500 mL in a normal adult, and (2) the increase in capillary transmural hydrostatic pressure causes a tremendously high transcapillary filtration rate.

For reasons to be described, a reflex activation of sympathetic nerves accompanies the transition from a recumbent to an upright position. However, Figure 10 2C shows how vasoconstriction from sympathetic activation is only marginally effective in ameliorating the adverse effects of gravity on the lower extremities. Arteriolar constriction can cause a greater pressure drop across arterioles, but this has only a limited effect on capillary pressure because venous pressure remains extremely high. Filtration will continue at a very high rate. In fact, the normal cardiovascular reflex mechanisms alone are incapable of dealing with upright posture without the aid of the "skeletal muscle pump." A person who remained upright without intermittent contraction of the skeletal muscles in the legs would lose consciousness in 10 20 minutes because of the decreased brain blood flow that would stem from diminished central blood volume, stroke volume, cardiac output, and arterial pressure.

The effectiveness of the skeletal muscle pump in counteracting venous blood pooling and edema formation in the lower extremities during standing is illustrated in Figure 10 2D and E. The compression of vessels during skeletal muscle contraction expels both venous blood and lymphatic fluid from the lower extremities (Figure 10 2D). Immediately after a skeletal muscle contraction, both veins and lymphatic vessels are relatively empty because their one-way valves prevent the back flow of previously expelled fluid (Figure 10 2E). Most important, the weight of the venous and lymphatic fluid columns is temporarily supported by the closed one-way valve leaflets. Consequently, venous pressure is drastically lowered immediately after skeletal muscle contraction and rises only gradually as veins refill with blood from the capillaries. Thus capillary pressure and transcapillary fluid filtration rate are dramatically reduced for some period after a skeletal muscle contraction. Periodic skeletal muscle contractions can keep the average value of venous pressure at levels that are only moderately above normal. This, in combination with an increased pressure drop across vasoconstricted arterioles, prevents capillary pressures from rising to intolerable levels in the lower extremities. Some transcapillary fluid filtration is still present, but the increased lymphatic flow resulting from the skeletal muscle pump is normally sufficient to prevent noticeable edema formation in the feet.

The actions of the skeletal muscle pump, however beneficial, do not completely prevent a rise in the average venous pressure and blood pooling in the lower extremities on standing. Thus, assuming an upright position upsets the cardiovascular system and elicits reflex cardiovascular adjustments, as shown in Figure 10 3.

As with all cardiovascular responses, the key to understanding the alterations associated with standing is to distinguish the primary disturbances from the compensatory responses. As shown in the top part of Figure 10 3, the immediate consequence of standing is an increase in both arterial and venous pressure in the lower extremities. The latter causes a major redistribution of blood volume out of the central venous pool. By the chain of events shown, the primary disturbances influence the cardiovascular centers by lessening the normal input from both the arterial and the cardiopulmonary baroreceptors.

The result of a decreased baroreceptor input to the cardiovascular centers will be reflex adjustments appropriate to increase blood pressure ie, decreased cardiac parasympathetic nerve activity and increased activity of the cardiovascular sympathetic nerves as shown in the bottom part of Figure 10 3. Heart rate and cardiac contractility will increase, as will arteriolar and venous constriction in most systemic organs (brain and heart excepted).

Heart rate and total peripheral resistance are higher when an individual stands than when the individual is lying down. Note that these particular cardiovascular variables are not directly influenced by standing but are changed by the compensatory responses. Stroke volume and cardiac output, conversely, are usually decreased below their recumbent values during quiet standing despite the reflex adjustments that tend to increase them. This is because the reflex adjustments do not quite overcome the primary disturbance on these variables caused by standing. This is in keeping with the general dictum that short-term cardiovascular compensations never completely correct the initial disturbance.

Mean arterial pressure is often found to increase when a person changes from the recumbent to the standing position. At first glance, this is a violation of many rules of cardiovascular system operation. How can a compensation be more than complete? Moreover, how is increased sympathetic activity compatible with higher than normal mean arterial pressure in the first place? In the case of standing, there are many answers to these apparent puzzles. First, the average arterial baroreceptor discharge rate can actually decrease in spite of a small increase in mean arterial pressure if there is simultaneously a sufficiently large decrease in pulse pressure. Second, mean arterial pressure determined by sphygmomanometry from the arm of a standing individual overestimates the mean arterial pressure actually being sensed by the baroreceptors in the carotid sinus region of the neck because of gravitational effects. Third, the influence on the medullary cardiovascular centers from cardiopulmonary receptors is being interpreted as a decrease in blood volume and may raise the arterial pressure by mechanisms shown in Figure 9 7A.

The kidney is especially susceptible to changes in sympathetic nerve activity, and consequently, as shown in Figure 10 3, every reflex alteration in sympathetic activity has influences on fluid balance that become important in the long term. Standing, which is associated with an increase in sympathetic tone, ultimately results in an increase in fluid volume. The ultimate benefit of this is that an increase in blood volume generally reduces the magnitude of the reflex alterations required to tolerate upright posture.

Responses to Long-Term Bed Rest (or Zero Gravity)

The cardiovascular system of an individual who is subjected to long-term bed rest undergoes a variety of adaptive changes that are quite similar to those experienced by people who travel outside of the earth's atmosphere at zero gravity. In both cases, the consequences of these adjustments are substantial.

The most significant immediate change that occurs upon assuming a recumbent position (or entering a gravity-free environment) is a shift of fluid from the lower extremities to the upper portions of the body. The consequences of this shift include distention of the head and neck veins, facial edema, nasal stuffiness, and decreases in calf girth and leg volume. In addition, the increase in central blood volume stimulates the cardiopulmonary mechanoreceptors, which influence renal function by neural and hormonal pathways to reduce sympathetic drive and promote fluid loss. The individual begins to lose weight and, within a few days, becomes hypovolemic (by normal earth standards).

When the bedridden patient initially tries to stand up (or when the space traveler reenters earth's gravitational field), the normal responses to gravity as described in Figure 10 3 are not as effective, primarily because of the substantial decrease in circulating blood volume. Upon standing, blood shifts out of the central venous pool into the peripheral veins, stroke volume falls and the individual often becomes dizzy and may faint due to a dramatic fall in blood pressure. This phenomenon is referred to as orthostatic or postural hypotension. Because there are other cardiovascular changes that may accompany bed rest (or space travel), complete reversal of this orthostatic intolerance may take several days or even weeks.

Efforts made to diminish the cardiovascular changes for the bedridden patient may include intermittent sitting up or tilting the bed to lower the legs and trigger fluid retention mechanisms. Efforts made in space to accomplish the same end may include exercise programs, lower body negative pressure devices and salt and water loading. (These interventions have met with limited success.)

Effect of Exercise

Responses to Acute Exercise

Physical exercise is one of the most ordinary yet taxing situations with which the cardiovascular system must cope. The specific alterations in cardiovascular function that occur during exercise depend on several factors including: (1) the type of exercise ie, whether it is predominantly "dynamic" (rhythmic or isotonic) or "static" (isometric); (2) the intensity and duration of the exercise; (3) the age of the individual; and (4) the level of "fitness" of the individual. The example shown in Figure 10 4 is typical of the cardiovascular alterations that might occur in a normal, untrained, middle-aged adult doing a dynamic-type exercise such as running or dancing. Note especially that heart rate and cardiac output increase greatly during exercise and that mean arterial pressure and pulse pressure also increase significantly. These alterations ensure that the increased metabolic demands of the exercising skeletal muscle are met by appropriate increases in skeletal muscle blood flow.

Many of the adjustments to exercise are due to a large increase in sympathetic activity, which results from the mechanisms outlined in Figure 10 5. One of the primary disturbances associated with the stress and/or anticipation of exercise originates within the cerebral cortex and exerts an influence on the medullary cardiovascular centers through corticohypothalamic pathways. This set-point-raising influence, referred to as the "central command," acts on the neural portion of the arterial baroreceptor system and causes mean arterial pressure to be regulated to a higher than normal level, as discussed in Chapter 9 (see Figure 9 7A). Also indicated in Figure 10 5 is the possibility that a second set-point-raising influence may reach the cardiovascular centers from chemoreceptors and mechanoreceptors in the active skeletal muscles. Such inputs would also contribute to the elevations in sympathetic activity and mean arterial pressure that accompany exercise.

A major primary disturbance on the cardiovascular system during dynamic exercise, however, is the great decrease in total peripheral resistance caused by metabolic vasodilator accumulation and decreased vascular resistance in active skeletal muscle. As indicated in Figure 10 5, decreased total peripheral resistance is a pressure-lowering disturbance that elicits a strong increase in sympathetic activity through the arterial baroreceptor reflex.

Although mean arterial pressure is above normal during exercise, the decreased total peripheral resistance causes it to fall below the elevated level to which it would be regulated by the set-point-raising influences on the cardiovascular center alone. The arterial baroreceptor reflex pathway responds to this circumstance with a large increase in sympathetic activity (see Figure 9 7B). Thus, the arterial baroreceptor reflex is responsible for a large portion of the increase in sympathetic activity that accompanies exercise despite the seemingly contradictory fact that arterial pressure is higher than normal. In fact, were it not for the arterial baroreceptor reflex, the decrease in total peripheral resistance that occurs during exercise would cause mean arterial pressure to fall well below normal.

As discussed in Chapter 9, and indicated in Figures 10 4 and 10 5, cutaneous blood flow may increase during exercise despite a generalized increase in sympathetic vasoconstrictor tone because thermal reflexes can override pressure reflexes in the special case of skin blood flow control. Temperature reflexes, of course, are usually activated during strenuous exercise to dissipate the excess heat being produced by the active skeletal muscles. Often cutaneous flow decreases at the onset of exercise (as part of the generalized increase in arteriolar tone from increased sympathetic vasoconstrictor activity) and then increases later during exercise as body heat and temperature build up.

In addition to the increases in skeletal muscle and skin blood flow, coronary blood flow increases substantially during strenuous exercise. This is primarily due to local metabolic vasodilation of coronary arterioles as a result of increased cardiac work and myocardial oxygen consumption.

Two important mechanisms that participate in the cardiovascular response to dynamic exercise are not shown in Figure 10 5. The first is the skeletal muscle pump, which was discussed in connection with upright posture. The skeletal muscle pump is a very important factor in promoting venous return during dynamic exercise and thus preventing the increased heart rate and cardiac contractility and therefore increased cardiac output from drastically lowering central venous pressure. The second factor is the respiratory pump, which also promotes venous return during exercise. Exaggerated respiratory movements that occur during exercise increase the effectiveness of the respiratory pump and thus enhance venous return and cardiac filling.

As indicated in Figure 10 4, the average central venous pressure does not change much, if at all, during strenuous dynamic exercise. This is because the cardiac output and the venous return curves are both shifted upward during exercise. Therefore, the cardiac output and venous return will be elevated without a significant change in central venous pressure. Thus, the increase in stroke volume that accompanies exercise largely reflects the increased myocardial contractility and increased ejection fraction with decreased end-systolic ventricular volume.

In summary, the profound cardiovascular adjustments to dynamic exercise shown in Figure 10 5 all occur automatically as a consequence of the operation of the normal cardiovascular control mechanisms. The tremendous increase in skeletal muscle blood flow is accomplished largely by increased cardiac output but also in part by diverting flow away from the kidneys and the splanchnic organs.

Static exercise (ie, isometric) presents a much different disturbance on the cardiovascular system than does dynamic exercise. As discussed in the previous section, dynamic exercise produces large reductions in total peripheral resistance because of local metabolic vasodilation in exercising muscles. Static efforts, even of moderate intensity, cause a compression of the vessels in the contracting muscles and a reduction in the blood flow through them. Thus, total peripheral resistance does not usually fall during strenuous static exercise and may even increase significantly. The primary disturbances on the cardiovascular system during static exercise seem to be set-point-raising inputs to the medullary cardiovascular centers from the cerebral cortex (central command) and from chemoreceptors and mechanoreceptors in the contracting muscle. These inputs result in another example of what is termed the "exercise pressor response."

Cardiovascular effects of static exercise include increases in heart rate, cardiac output, and arterial pressure, all of which are the result of increases in sympathetic drive. Static exercise, however, produces less of an increase in heart rate and cardiac output and more of an increase in diastolic, systolic, and mean arterial pressure than does dynamic exercise. Because of the higher afterload on the heart during static exercise, cardiac work is significantly higher than during dynamic exercise.

The time course of recovery of the various cardiovascular variables after a bout of exercise depends on many factors, including the type, duration, and intensity of the exercise as well as the overall fitness of the individual. Muscle blood flow normally returns to a resting value within a few minutes after dynamic exercise. However, if an abnormal arterial obstruction prevents a normal active hyperemia from occurring during dynamic exercise, the recovery will take much longer than normal. After isometric exercise, muscle blood flow often rises to near maximum levels before returning to normal with a time course that varies with the duration and intensity of the effort. Part of the increase in muscle blood flow that follows isometric exercise might be classified as reactive hyperemia in response to the blood flow restriction caused by compressional forces within the muscle during the exercise.

Responses to Chronic Exercise

Physical training or "conditioning" produces substantial beneficial effects on the cardiovascular system. The specific alterations that occur depend on the type of exercise, the intensity and duration of the training period, the age of the individual, and his or her original level of fitness.

In general, however, repeated physical exercise over a period of several weeks is associated with an increase in the individual's work capacity. Cardiovascular alterations associated with conditioning may include increases in circulating blood volume, decreases in heart rate, increases in cardiac stroke volume, and decreases in arterial blood pressure at rest. During exercise, a trained individual will be able to achieve a given workload and cardiac output with a lower heart rate and higher stroke volume than will be possible by an untrained individual. These changes produce a general decrease in myocardial oxygen demand and an increase in the cardiac reserve (potential for increasing cardiac output) that can be called on during times of stress. Ventricular chamber enlargement often accompanies dynamic exercise conditioning regimes (endurance training) whereas increases in myocardial mass and ventricular wall thickness are more pronounced with static exercise conditioning regimes (strength training). These structural alterations improve the pumping capabilities of the myocardium.² Deconditioning occurs with the cessation of the exercise program and the changes rapidly reverse.

It is clear that exercise and physical conditioning can significantly reduce the incidence and mortality of cardiovascular disease. While studies have not established specific mechanisms for these beneficial effects, there is a positive correlation between physical inactivity and the incidence rate and intensity of coronary heart disease. It is increasingly evident that recovery from a myocardial infarction or cardiac surgery is enhanced by an appropriate increase in physical activity. The benefits of cardiac rehabilitation programs include improvement in various indices of cardiac function as well as improvements in physical work capacity, percent body fat, serum lipids, psychological sense of well-being and quality of life.

² However, as will be described in the next chapter, ventricular chamber enlargement and myocardial hypertrophy are not always hallmarks of improved cardiac performance but may be adaptive responses to various pathological states which, if extreme, may not be helpful.

Age-Dependent Cardiovascular Changes

Up to this point, the cardiovascular system of a normal adult has been described. However, there are some important cardiovascular alterations that accompany birth, growth and aging. The material in the following section is a brief overview of these changes.

Fetal Circulation & Changes at Birth

During fetal development, the exchange of nutrients, gases, and waste products between fetal and maternal blood occurs in the placenta. This exchange occurs by diffusion between separate fetal and maternal capillaries without any direct connection between the fetal and maternal circulations. From a hemodynamic standpoint, the placenta represents a temporary additional large systemic organ for both the fetus and the mother. The fetal component of the placenta has a low vascular resistance and receives a substantial portion of the fetal cardiac output.

Blood circulation in the developing fetus completely bypasses the collapsed fetal lungs. No blood flows into the pulmonary artery because the vascular resistance in the collapsed fetal lungs is essentially infinite. By the special structural arrangements shown in Figure 10 6, the fetal right and left hearts actually operate in parallel to pump blood through the systemic organs and the placenta. As shown in Figure 10 6A, fetal blood returning from the systemic organs and placenta fills both the left and right hearts together because of an opening in the intraatrial septum called the foramen ovale. As indicated in Figure 10 6B, blood that is pumped by the fetal right heart does not enter the occluded pulmonary circulation but rather is diverted into the aorta through a vascular connection between the pulmonary artery and the aorta called the ductus arteriosis.

An abrupt decrease in pulmonary vascular resistance occurs at birth with the onset of lung ventilation. This permits blood to begin flowing into the lungs from the pulmonary artery and tends to lower pulmonary arterial pressure. Meanwhile, total systemic vascular resistance increases greatly because of the interruption of flow through the placenta. This causes a rise in aortic pressure, which retards or even reverses the flow through the ductus arteriosis. Through mechanisms that are incompletely understood but clearly linked to a rise in blood oxygen tension, the ductus arteriosis gradually constricts and completely closes over time, normally ranging from hours to a few days. The circulatory changes that occur at birth tend to simultaneously increase the pressure afterload on the left heart and decrease that on the right. This indirectly causes left atrial pressure to increase above that in the right atrium so that the pressure gradient for flow through the foramen ovale is reversed. Reverse flow through the foramen ovale is, however, prevented by a flaplike valve that covers the opening in the left atrium. Normally, the foramen ovale eventually is closed permanently by the growth of fibrous tissue.

Pediatric Cardiovascular Characteristics

Cardiovascular variables change significantly between birth and adulthood. The normal neonate has, by adult standards, a high resting heart rate (average of 140 beats/min) and a low arterial blood pressure (average of 60/35 mmHg). These values rapidly change over the first year (to 120 beats/min and 100/65 mmHg, respectively). By the time the child enters adolescence, these values are near adult levels.

Pulmonary vascular resistance decreases precipitously at birth as described above and then continues to decline during the first year, at which time pulmonary pressures resemble adult levels. These resistance changes appear to be due to a progressive remodeling of the microvascular arterioles from thick-walled, small diameter vessels to thin-walled large diameter microvessels.

It is noteworthy that distinct differences between right and left ventricular mass and wall thickness develop only after birth. Presumably they arise because of a hypertrophic response of the left ventricle to the increased afterload it must assume at birth. Accordingly, the electrocardiogram of children shows an early right ventricular dominance (electrical axis orientation) that converts to the normal left ventricular dominance during childhood.

Heart murmurs are also quite common in childhood and have been reported to be present in as many as 50% of healthy children. Most of these murmurs fall in the category of "innocent" murmurs resulting from normal cardiac tissue vibrations, high flow through valves, and thin chest walls that make noises from the vasculature easy to hear. Less than 1% of them result from various congenital heart defects.

Growth and development of the vascular system parallels growth and development of the body with most of the local and reflex regulatory mechanisms operational shortly after birth.

Cardiovascular Changes with Normal Aging

In general, as persons get older, they get slower, stiffer, and drier. Connective tissue becomes less elastic, capillary density decreases in many tissues, mitotic activity of dividing cells becomes slower, and fixed postmitotic cells (such as nerve and muscle fibers) are lost. While these changes do not, in general, alter the basic physiological processes, they do have an influence upon the rate at which various homeostatic mechanisms operate.

Age-dependent changes that occur in the heart include: (1) a decrease in the resting and maximum cardiac index, (2) a decrease in the maximum heart rate, (3) an increase in the contraction and relaxation time of the heart muscle, (4) an increase in the myocardial stiffness during diastole, (5) a decrease in number of functioning myocytes, and (6) an accumulation of pigment in the myocardial cells.

Changes that occur in the vascular bed with age include a decrease in capillary density in some tissues, a decrease in arterial compliance, and an increase in total peripheral vascular resistance. These changes combine to produce the age-dependent increases in arterial pulse pressure and mean arterial pressure that were discussed in Chapter 6. The increases in arterial pressure impose a greater afterload upon the heart, and this may be partially responsible for the age-dependent decreases in cardiac index.

Arterial baroreceptor-induced responses to changes in blood pressure are blunted with age. This is due in part to a decrease in afferent activity from the arterial baroreceptors because of the age-dependent increase in arterial rigidity. In addition, the total amount of norepinephrine contained in the sympathetic nerve endings of the myocardium decreases with age, and the myocardial responsiveness to catecholamines declines. Thus, the efferent component of the reflex is also compromised. These changes may partially account for the apparent age-dependent sluggishness in the responses to postural changes and recovery from exercise.

It is important (although often difficult) to separate age-dependent alterations from disease-induced changes in physiological function. Cardiovascular diseases are the major cause of death in an aging population. Atherosclerosis and hypertension are the primary culprits in many populations. These "diseases" lack the universality necessary to be categorized as aging processes but generally occur with increasing incidence in the older population. Pharmacological interventions and reduction of risk factors (smoking, obesity, high fat or high sodium diets, inactivity) by modification of lifestyle can alter the incidence, intensity, and progression of these diseases. It is also possible that some of the previously mentioned interventions may prevent early expression of some of the normal aging processes and prolong the life span of a given individual. No practical intervention, however, is currently available that will increase the maximum potential life span of humans.

Effect of Gender

There are a few well-documented gender-dependent differences in the cardiovascular system. Compared with age-matched men, premenopausal women have a lower left ventricular mass to body mass ratio, which may reflect a lower cardiac afterload in women. This may result from their lower arterial blood pressure, greater aortic compliance, and improved ability to induce vasodilatory mechanisms (such as endothelial-dependent flow-mediated vasodilation). These differences are thought to be related to protective effects of estrogen and may account for the lowered risk of premenopausal women for developing cardiovascular disease. After menopause, these gender differences disappear. In fact, older women with ischemic heart disease often have a worse prognosis than men.

There are also gender-dependent differences in cardiac electrical properties. Women have lower intrinsic heart rates and longer QT intervals than do men. They are at greater risk for developing long-QT syndrome and torsades de pointes. They are also twice as likely as men to have atrioventricular nodal re-entry tachycardias.

However, it should be noted that most basic cardiovascular physiological processes are not greatly influenced by gender and that individual differences in physiological responses within genders are usually as large as, or larger than, differences between genders.

Key Concepts

Cardiovascular responses to physiological stresses should be evaluated in terms of the initial effects of the primary disturbance and the subsequent effects of the reflex compensatory responses.

Changes in intrathoracic pressure due to respiratory activity have significant effects on the cardiovascular system, primarily by influencing venous return and cardiac filling.

Gravity, and hence body position, has a significant effect on the cardiovascular system, and various reflex compensatory mechanisms are required to overcome venous pooling that accompanies the upright position.

Long-term bed rest causes decreases in circulating blood volume that contributes to orthostatic hypotension.

The primary cardiovascular disturbances of exercise (central command and muscle vasodilation) evoke immediate reflex compensatory activity, which permits major changes in muscle blood flow and cardiac output.

Chronic exercise (training) evokes compensatory adjustments in cardiovascular characteristics and muscle metabolic processes, permitting greater exercise efficiency.

Circulatory pathways in the fetus are significantly different from those of the newborn and change abruptly at birth with the first breath.

Aging results in decreases in the maximal capabilities of cardiovascular responses that are distinct from any disease processes.

Gender influences several cardiovascular characteristics and disease susceptibility particularly before the age of menopause in women.

Study Questions

10 1. How are the thin-walled capillaries in the feet able to withstand pressures greater than 100 mmHg in a standing individual without rupturing?

10 2. Soldiers faint when standing at attention on a very hot day more often than on a cooler day. Why?

10 3. For several days after an extended period of bed rest, patients often become dizzy when they stand upright quickly because of an exaggerated transient fall in arterial pressure (orthostatic hypotension). Why might this be so?

10 4. Vertical immersion to the neck in tepid water produces a diuresis in many individuals. What mechanisms might account for this phenomenon?

10 5. How is the decrease in skeletal muscle vascular resistance evident from the data presented in Figure 10 4?

10 6. Is a decrease in total peripheral resistance implied in Figure 10 4?

10 7. What in Figure 10 4 implies increased sympathetic activity?

10 8. From the information given in Figure 10 4,

a. Calculate the resting and exercising stroke volumes (SVs).

b. Calculate the resting and exercising end-diastolic volumes (EDVs).

c. Calculate the resting and exercising end-systolic volumes (ESVs).

d. Construct a sketch that indicates, as accurately as possible, how this exercise affects the left ventricular volume-pressure cycle.

10 9. The "iron lung," used to help polio victims breathe in the mid 20th century, applied an external intermittent negative pressure to the patient's thoracic cavity. How is this better than positive pressure ventilation of the patient's lungs?

10 10. Blood pressure can rise to extremely high levels during strenuous isometric exercise maneuvers like weight lifting. Why?

See answers.