The heart is a hollow, four-chambered muscular organ approximately the size of a fist. It is positioned obliquely in the middle compartment of the mediastinum of the chest, just behind the sternum (Figure 9-1). Approximately two-thirds of the heart lies to the left of the midline of the sternum between the points of attachment of the second through the sixth ribs. The apex of the heart is formed by the tip of the left ventricle and lies just above the diaphragm at the level of the fifth intercostal space to the left. The base of the heart is formed by the atria and projects to the patient’s right lying just below the second rib. It is level with the second rib below the sternum. Posteriorly, the heart rests on the bodies of the fifth to the eighth thoracic vertebrae. Because of its position between the sternum and the spine, rhythmic compression of the heart can maintain blood flow during cardiopulmonary resuscitation.

Externally, surface grooves called sulci mark the boundaries of the heart chambers. Compared with the ventricles, the atria are small, thin-walled chambers that contribute little to the total pumping activity of the heart.

The heart is enclosed in a double-walled sac called the pericardium. The outer fibrous layer consists of tough connective tissue. The inner serous layer is thinner and more delicate. The structure of the pericardium can be summarized as follows:

A thin layer of fluid called the pericardial fluid separates the two layers of the serous pericardium. This layer of fluid helps minimize friction as the heart contracts and expands within the pericardium. Inflammation of the pericardium results in a clinical condition called pericarditis. An abnormal amount of fluid can accumulate between the layers resulting in a pericardial effusion. A large pericardial effusion may affect the pumping function of the heart resulting in a cardiac tamponade. A cardiac tamponade compresses the heart muscle leading to a serious decrease in blood flow to the body, which ultimately may lead to shock and death.

The heart wall consists of three layers: (1) outer epicardium, (2) middle myocardium, and (3) inner endocardium. The myocardium composes the bulk of the heart muscle and consists of bands of involuntary striated muscle fibers. The contraction of these muscle fibers creates the pumplike action needed to move blood throughout the body.

Support for the four interior chambers and valves of the heart is provided by four atrioventricular rings, which form a fibrous “skeleton.” Each ring is composed of dense connective tissue termed anulus fibrosus cordis. This connective tissue, besides providing an anchoring structure for the heart valves, electrically isolates the atria from the ventricle. No impulses can be transmitted through the heart tissue from the atria to the ventricles.

The two atrial chambers are thin-walled “cups” of myocardial tissue, separated by an interatrial septum. On the right side of the interatrial septum is an oval depression called the fossa ovalis cordis, which is the remnant of the fetal foramen ovale, the shunt that allowed blood to enter the left atrium from the right atrium before birth. In addition, each atrium has an appendage, or auricle, the function of which is unknown. In the presence of cardiac dysrhythmias, blood flow can become stagnant on these appendages leading to the formation of thrombi.

The two lower heart chambers, or ventricles, make up the bulk of the heart’s muscle mass and do most of the pumping that circulates the blood (Figure 9-2). The mass of the left ventricle is normally about two-thirds larger than the mass of the right ventricle and has a spherical appearance when viewed in anteroposterior cross section. The right ventricle is thin-walled and oblong, forming a pocket-like attachment to the left ventricle. Because of this relationship, contraction of the left ventricle pulls in the right ventricular wall, aiding its contraction. The effect, termed left ventricular aid, explains why some forms of right ventricular failure are less harmful than might be expected. The right and left ventricles are separated by a muscle wall termed the interventricular septum (see Figure 9-2).

The valves of the heart are flaps of fibrous tissue firmly anchored to the anulus fibrosus cordis (Figure 9-3). Because they are located between the atria and ventricles, they are called atrioventricular valves. The valve between the right atrium and ventricle is called the tricuspid valve. The valve between the left atrium and ventricle is the bicuspid, or mitral, valve. The atrioventricular valves close during systole (contraction of the ventricles), preventing backflow of blood into the atria. Closure of these valves provides a critical period of isovolemic contraction, during which chamber pressures quickly increase just before ejection of the blood.

The free ends of the atrioventricular valves are anchored to papillary muscles of the endocardium by the chordae tendineae cordis (see Figure 9-2). During systole, papillary muscle contraction prevents the atrioventricular valves from swinging upward into the atria. Damage to either the chordae tendineae cordis or the papillary muscles can impair function of the atrioventricular valves and cause leakage upward into the atria.

Common valve problems include regurgitation and stenosis. Regurgitation is the backflow of blood through an incompetent or a damaged valve. Stenosis is a pathologic narrowing or constriction of a valve outlet, which causes increased pressure in the proximal chamber and vessels. Both conditions affect cardiac performance. In mitral stenosis, high pressures in the left atrium back up into the pulmonary circulation. This can cause pulmonary edema and a diastolic murmur (see Chapter 15).

A set of semilunar valves separates the ventricles from their arterial outflow tracts, the pulmonary artery and the aorta (see Figure 9-3). Consisting of three half-moon–shaped cusps attached to the arterial wall, these valves prevent backflow of blood into the ventricles during diastole (or when the chambers of the heart fill with blood). The pulmonary valve is at the outflow tract of the right ventricle. During the cardiac contraction (systole), blood is ejected out of the heart and to the lungs through the right valves and to the body through the left valves. Similar to the atrioventricular valves, the semilunar valves can leak (regurgitation) or become obstructed (stenosis).

Similar to the lungs, the heart has its own circulatory system, which is called the coronary circulation. However, in contrast to the lungs, the heart has a high metabolic rate, which requires more blood flow per gram of tissue weight than any other organ except the kidney. To meet these needs, the coronary circulation provides an extensive network of branches to all myocardial tissue (Figure 9-4).

Two main coronary arteries, a left and a right, arise from the root of the aorta. Because of their position underneath the aortic semilunar valves (see Figure 9-4), the coronary arteries get the maximal pulse of pressure generated by contraction of the left ventricle. Blood flows through the coronary arteries only during ventricular diastole (relaxation). A healthy heart muscle requires about of the blood supply of the body to function properly. As might be expected, partial obstruction of a coronary artery may lead to tissue ischemia (decreased oxygen [O₂] supply), a clinical condition called angina pectoris. Complete obstruction may cause tissue death or infarct, a condition called myocardial infarction.

For a description of the major branches of the coronary arteries and their areas of vascularization, see Table 9-1 and Figure 9-4. After passing through the capillary beds of the myocardium, the venous blood is collected by the coronary veins that closely parallel the arteries (see Figure 9-4). These veins gather together into a large vessel called the coronary sinus, which passes left to right across the posterior surface of the heart. The coronary sinus empties into the right atrium between the opening of the inferior vena cava and the tricuspid valve.

In addition to these major routes for return blood flow, some coronary venous blood flows back into the heart through the thebesian veins. The thebesian veins empty directly into all the heart chambers. Any blood coming from the thebesian veins that enters the left atrium or ventricle mixes with arterial blood coming from the lungs. Whenever venous blood mixes with arterial blood, the overall O₂ content decreases. Because the thebesian veins bypass, or shunt, around the pulmonary circulation, this phenomenon is called an anatomic shunt. When combined with a similar bypass in the bronchial circulation (see Chapter 8), these normal anatomic shunts account for approximately 2% to 3% of the total cardiac output.

Microanatomy of the Heart Muscle

Understanding how cardiac muscle contracts requires knowledge of the microanatomy of the heart. In contrast to the long, cylindrical, multinucleated skeletal muscle fibers, cardiac cells are short, fat, branched, and interconnected. As seen under the microscope, myocardial muscle fibers are approximately 15 µm wide × 100 µm long. Individual fibers are enclosed in a membrane called the sarcolemma, which is surrounded by a rich capillary network (Figure 9-5).

Cardiac fibers are separated by irregular transverse thickenings of the sarcolemma called intercalated discs. These discs provide structural support and aid in electrical conduction between fibers. Each muscle fiber consists of many smaller units called myofibrils, which contain repeated structures approximately 2 µm in size termed sarcomeres. Within the sarcomeres are contractile protein filaments responsible for shortening the myocardium during systole. These proteins are of two types: thick filaments composed mainly of myosin and thin filaments composed mostly of actin.

According to the sliding filament theory, myocardial cells contract when actin and myosin combine to form reversible bridges between these thick and thin filaments. These bridges cause filaments to slide over one another, shortening the sarcomere and muscle fibers as a whole.

In principle, the tension developed during myocardial contraction is directly proportional to the number of cross-bridges between the actin and myosin filaments. The number of cross-bridges is directly proportional to the length of the sarcomere. This principle underlies Starling’s law of the heart, also known as the Frank-Starling law. According to this law, the more a cardiac fiber is stretched, the greater the tension it generates when contracted.

The Frank-Starling law holds true up to a sarcomere length of 2.2 µm. Beyond this length, the actin and myosin filaments become partially disengaged, and fewer cross-bridges can be formed. With fewer cross-bridges, the overall tension developed during contraction is less. This relationship is extremely important and is explored later in the discussion of the heart as a pump.

Vascular System

The vascular system has two major subdivisions: the systemic vasculature and the pulmonary vasculature. The systemic vasculature begins with the aorta on the left ventricle and ends in the right atrium. The pulmonary vasculature begins with the pulmonary trunk out of the right ventricle and ends in the left atrium. The blood flow to and from the heart is depicted in Figure 9-6.

Venous, or deoxygenated, blood from the head and upper extremities enters the right atrium from the superior vena cava, and blood from the lower body enters from the inferior vena cava. From the right atrium, blood flows through the tricuspid valve into the right ventricle. The right ventricle pumps the blood through the pulmonary valve, into the pulmonary arteries, and on to the lungs.

Arterial, or oxygenated, blood returns to the left atrium through the pulmonary veins. The left atrium pumps blood through the mitral valve into the left ventricle. The blood is pumped through the aortic valve and into the aorta. From the aorta, the blood flows out to the tissues of the upper and lower body. From the capillary network of the various body tissues, the deoxygenated venous blood returns to the right ventricle through the superior and inferior venae cavae.

Systemic Vasculature

The systemic vasculature has three major components: (1) arterial system, (2) capillary system, and (3) venous system. These vessels regulate not only the amount of blood flow per minute (cardiac output) but also the distribution of blood to organs and tissues. To achieve this function, each component has a unique structure and plays a different role in the circulatory system as a whole.

The arterial system consists of large, highly elastic, low-resistance arteries and small, muscular arterioles of varying resistance. With their high elasticity, the large arteries help transmit and maintain the head of pressure generated by the heart. Together, the large arteries are called conductance vessels. Just as faucets control the flow of water into a sink, the smaller arterioles control blood flow into the capillaries. Arterioles provide this control by varying their flow resistance. Arterioles play a major role in the distribution and regulation of blood pressure and are referred to as resistance vessels.

The vast capillary system, or microcirculation, maintains a constant exchange of nutrients and waste products for the cells and tissues of the body. For this reason, the capillaries are commonly referred to as exchange vessels. Figure 9-7 shows the structure of a typical capillary network. Blood flows into the network by an arteriole and out through a venule. A direct communication between these vessels is called an arteriovenous anastomosis. When open, an arteriovenous anastomosis allows arterial blood to shunt around the capillary bed and flow directly into the venules. Downstream from the arteriovenous anastomosis, the arteriole divides into terminal arterioles, which branch further into thoroughfare channels and true capillaries.

Capillaries have smooth muscle rings at their proximal ends, called precapillary sphincters. Contraction of these sphincters decreases blood flow in that area, whereas relaxation increases perfusion. In combination, these various channels, sphincters, and bypasses allow precise control over the direction and amount of blood flow to a given area of tissue.

The venous system consists of small, expandable venules and veins and larger, more elastic veins. Besides conducting blood back to the heart, these vessels act as a reservoir for the circulatory system. At any given time, the veins and venules hold approximately three-fourths of the body’s total blood volume. The volume of blood held in this reservoir can be rapidly changed as needed simply by altering the tone of these vessels. By quickly changing its holding capacity, the venous system can match the volume of circulating blood to that needed to maintain adequate tissue perfusion. The components of the venous system, especially the small, expandable venules and veins, are termed capacitance vessels.

The venous system must overcome gravity to return blood to the heart. The following four mechanisms combine to aid venous return to the heart: (1) sympathetic venous tone; (2) skeletal muscle pumping, or “milking” (combined with venous one-way valves); (3) cardiac suction; and (4) thoracic pressure differences caused by respiratory efforts.

The last mechanism is often called the thoracic pump. As an aid to venous return, the thoracic pump is particularly important to respiratory therapists (RTs) because artificial ventilation with positive pressure reverses normal thoracic pressure gradients. Positive pressure ventilation impedes, rather than assists, venous return. As long as blood volume, cardiac function, and vasomotor tone are adequate, positive pressure ventilation has a minimal effect on venous return. Patients who are hypovolemic or in cardiac failure are vulnerable to a reduction in cardiac output when positive pressure ventilation is applied to the lungs.

Although the heart is a single organ, it functions as two separate pumps. The right side of the heart generates a pressure of approximately 25 mm Hg to drive blood through the low-resistance, low-pressure pulmonary circulation. The left side of the heart normally generates pressures of about 120 mm Hg to propel blood through the higher pressure, high-resistance systemic circulation.

Vascular Resistance

Similar to the movement of any fluid through tubes, blood flow through the vascular system is opposed by frictional forces (based on Poiseuille’s law). The sum of all frictional forces opposing blood flow through the systemic circulation is called systemic vascular resistance (SVR). SVR must equal the difference in pressure between the beginning and the end of the circuit, divided by the flow. The beginning pressure for the systemic circulation is the mean aortic pressure; ending pressure equals right atrial pressure or central venous pressure (CVP). Flow for the system as a whole equals the cardiac output. SVR can be calculated by the following formula:

< ?xml:namespace prefix = "mml" />SVR=Mean aortic pressure−Right atrial pressureCardiac output

Given a normal mean aortic pressure of 90 mm Hg, a mean right atrial pressure of approximately 4 mm Hg, and a normal cardiac output of 5 L/min, normal SVR is computed as follows:

SVR=90 mm Hg−4 mm Hg5 L/min=17.2 mm Hg/L/min*

The same concepts can be used to compute flow resistance in the pulmonary circulation. Beginning pressure for the pulmonary circulation is the mean pulmonary artery pressure; ending pressure equals left atrial pressure. Flow for the pulmonary circulation is the same as it is for the systemic system, which equals the cardiac output. Pulmonary vascular resistance (PVR) can be calculated by using the following formula:

PVR=Mean pulmonary artery pressure−Left atrial pressureCardiac output

Given a normal mean pulmonary artery pressure of approximately 16 mm Hg and a normal mean left atrial pressure of 8 mm Hg, normal PVR is computed as follows:

PVR=16 mm Hg−8 mm Hg5L/min=1.6 mm Hg/L/min*

*Multiply by 80 to convert to dynes-sec/cm⁵.

Resistance to blood flow in the pulmonary circulation is normally much less than it is in the systemic circulation. The pulmonary vasculature is characterized as a low-pressure, low-resistance circulation.

Determinants of Blood Pressure

A healthy cardiovascular system maintains sufficient pressure to propel blood throughout the body. The first priority of the cardiovascular system is to keep perfusion pressures to tissues and organs normal, even under changing conditions. If the equation for computing SVR is rearranged by deleting the normally low atrial pressure, the average blood pressure in the circulation is directly related to both cardiac output and flow resistance:

Mean arterial pressure (MAP)=Cardiac output×Vascular resistance

With a constant rate and force of cardiac contractions, cardiac output (blood flow per minute) is approximately equal to the circulating blood volume. Under similar conditions, vascular resistance varies inversely with the size of the blood vessels (i.e., the capacity of the vascular system). All else being constant, MAP is directly related to the volume of blood in the vascular system and inversely related to its capacity:

MAP=VolumeCapacity

Based on this relationship, MAP is regulated by the following: changing the volume of circulating blood, changing the capacity of the vascular system, or changing both. Volume changes can reflect absolute changes in total blood volume, such as changes resulting from hemorrhagic shock or blood transfusion. Alternatively, changes in “relative” volume can occur when vascular space increases or decreases. Vascular space decreases when vasoconstriction (constriction of the smooth muscles in the peripheral blood vessels) occurs; this causes blood pressure to increase even though blood volume is the same. Vascular space increases when vasodilation (relaxation of the smooth muscles in the arterioles) occurs; this causes blood pressure to decrease even though blood volume has not changed.

In a normal adult, MAP ranges from 80 to 100 mm Hg. When MAP decreases to significantly less than 60 mm Hg, perfusion to the brain and the kidneys is severely compromised, and organ failure may occur in minutes.

To avoid organ and tissue damage and to maintain adequate perfusion pressures under changing conditions, the cardiovascular system balances relative volume and resistance. When a person exercises, the circulating blood volume undergoes a relative increase, but blood pressure remains near normal; this is because the skeletal muscle vascular beds dilate, causing a large increase in system capacity. However, when blood loss occurs, as with hemorrhage, the system capacity is decreased by constriction of the peripheral vessels. Perfusion pressures are kept near normal until the volume loss is extreme.

Regulation of blood flow and pressure is much more complex than is suggested by these simplified equations. Cardiovascular control is achieved by a complex array of integrated functions. Some of these functions are explained subsequently.

Control of the Cardiovascular System

The cardiovascular system is responsible for transporting metabolites to and from the tissues under various conditions and demands. It must act in a highly coordinated fashion. Coordination is achieved by integrating the functions of the heart and vascular system. The goal is to maintain adequate perfusion to all tissues according to their needs.

The cardiovascular system regulates blood flow mainly by altering the capacity of the vasculature and the volume of blood it holds. The heart plays only a secondary role in regulating blood flow. In essence, the vascular system tells the heart how much blood it needs, rather than the heart dictating what volume of blood the vascular system will receive.

These integrated functions involve local and central neural control mechanisms. Local, or intrinsic, controls operate independently, without central nervous system control. Intrinsic control alters perfusion under normal conditions to meet metabolic needs. Central, or extrinsic, control involves both the central nervous system and circulating humoral agents. Extrinsic control mechanisms maintain a basal level of vascular tone. However, central control mechanisms take over when the competing needs of local vascular beds must be coordinated. Knowledge of vascular regulatory mechanisms and factors controlling cardiac output is essential to understanding how the cardiovascular system responds under both normal and abnormal conditions.

Regulation of Cardiac Output

The heart, similar to the vascular system, is regulated by both intrinsic and extrinsic factors. These mechanisms act together, along with vascular control, to ensure that the output of the heart matches the different needs of the tissues.

The total amount of blood pumped by the heart per minute is called the cardiac output. Cardiac output is simply the product of the heart rate (HR) and the volume ejected by the left ventricle on each contraction, or stroke volume (SV):

Cardiac output=HR×SV

A normal resting cardiac output of approximately 5 L/min can be calculated by substituting a normal HR (70 contractions/min) and SV (75 mL, or 0.075 L, per contraction):

Cardiac output=70 beats/min×0.075 L/beat=5.25 L/min

This is a hypothetical average because actual cardiac output varies considerably in health and disease states and according to a subject’s sex, height, and weight.

Regardless of an individual’s state of health or disease, a change in cardiac output must involve a change in SV, a change in HR, or both. SV is affected primarily by intrinsic control of three factors: (1) preload, (2) afterload, and (3) contractility (all three factors are discussed subsequently). HR is affected primarily by extrinsic or central control mechanisms.

Changes in Stroke Volume

SV is the volume of blood ejected by the left ventricle during each contraction, or systole. The heart does not eject all of the blood it contains during systole. Instead, a small volume, called the end-systolic volume (ESV), remains behind in the ventricles. During the resting phase, or diastole, the ventricles fill to a volume called the end-diastolic volume (EDV).

SV equals the difference between the EDV and the ESV:

SV=EDV−ESV

In a healthy man at rest, the EDV ranges from 110 to 120 mL. Given a normal SV of approximately 70 mL, a normal ejection fraction (EF), or proportion of the EDV ejected on each stroke, can be calculated as follows:

EF=SVEDV=70ml110ml=0.64 or 64%

On each contraction, a healthy heart ejects approximately two-thirds of its stored volume. Decreases in EF are normally associated with a weakened myocardium (heart failure) or decreased contractility or both. When the EF decreases to 30% or less, a person’s exercise tolerance becomes severely limited.

As shown in Figure 9-8, an increase in SV occurs when either the EDV increases or the ESV decreases. Conversely, a decrease in SV occurs when either the EDV decreases or the ESV increases. This relationship is key to understanding regulation of cardiac output.

The heart’s ability to change SV solely according to the EDV is an intrinsic regulatory mechanism based on the Frank-Starling law. Because the EDV corresponds to the initial stretch, or tension, placed on the ventricle, the greater the EDV (up to a point), the greater the tension developed on contraction, and vice versa. This concept is similar to stretching a rubber band—the greater the stretch (up to a point), the greater the contractile force.

In clinical practice, this initial ventricular stretch is called preload, whereas the tension of contraction is equivalent to SV. Figure 9-9 applies the Frank-Starling law to ventricular function by plotting ventricular stretch against SV. Ventricular stretch is directly proportional to EDV, and EDV is directly related to the pressure difference across the ventricle wall. Preload can be measured indirectly as the ventricular end-diastolic pressure.

 Rule of Thumb

Increases in preload result in increased SV in the healthy heart.

Another major factor affecting SV is the force against which the heart must pump, which is called afterload. Afterload represents the sum of all external factors that oppose ventricular ejection. The factors can be summarized as (1) the tension in the ventricular wall and (2) peripheral resistance or impedance. In clinical practice, PVR on the right and SVR on the left are indirect indicators of ventricular afterload. In other words, the greater the resistance to blood flow out of the ventricles, the greater is the afterload.

All else being constant, the greater the afterload on the ventricles, the harder it is for the ventricles to eject their volume. For a given EDV, an increase in afterload causes the volume remaining in the ventricle after systole (ESV) to increase. If the EDV remains constant while the ESV increases, the SV (EDV − ESV) decreases (see Figure 9-8). Normally, however, the healthy heart muscle responds to increased afterload by altering its contractility.

 Rule of Thumb

Increases in afterload can decrease SV, especially in the failing heart.

Contractility represents the amount of systolic force exerted by the heart muscle at any given preload. At a given preload (EDV), an increase in contractility results in an increased EF, a decreased ESV, and an increased SV. Conversely, a decrease in contractility results in a decreased EF, an increased ESV, and a decreased SV.

Changes in contractility affect the slope of the ventricular function curve (Figure 9-10; see Figure 9-9). A higher SV for a given preload (increased slope) indicates a state of increased contractility, often referred to as positive inotropism. The opposite is also true. A lower SV for a given preload indicates decreased contractility, referred to as negative inotropism. Drugs that increase contractility of the heart muscle are called positive inotropes; drugs that decrease contractility are negative inotropes.

In addition to local mechanisms, cardiac contractility is influenced by neural control, circulating hormonal factors, and certain medications. Whether local or central in origin, these factors all influence the reactivity of contractile proteins, mainly by affecting calcium metabolism in the sarcomere. Typically, neural or drug-mediated sympathetic stimulation has a positive inotropic effect. Conversely, parasympathetic stimulation exerts a negative inotropic effect. Profound hypoxia and acidosis impair myocardial metabolism and decrease cardiac contractility.

 Rule of Thumb

Hypoxia and acidosis decrease cardiac contractility and output.

Changes in Heart Rate

The last factor influencing cardiac output is heart rate (HR). In contrast to the factors controlling SV, the factors affecting HR are mainly of central origin (i.e., neural or hormonal). Factors that increase HR are called positive chronotropic factors. Likewise, factors that decrease HR are called negative chronotropic factors.

Mini Clini

Effect of Increased Afterload on Cardiac Output in a Normal Heart

Afterload is the force against which the heart works to eject its SV. Afterload can be thought of as outflow resistance. As afterload increases, the SV ejected by the ventricle decreases, assuming that the contractility of the heart (force with which the heart contracts) remains constant.

 Problem

During exercise, a healthy person’s blood pressure increases considerably, indicating that the afterload has increased. Yet the SV and cardiac output in a healthy heart do not decrease. Why is this so?

Discussion

When afterload increases, the initial ventricular contractions that experience the increased afterload produce smaller SVs; this causes more blood to remain in the ventricle at the end of systole (i.e., ESV is increased). During the subsequent diastole, blood rushes in from the atria to fill the ventricles, and because of the higher than normal ESV, the ventricle becomes more distended and stretched than before. Healthy heart muscle responds to increased stretch in a way described by the Frank-Starling law; that is, the heart now contracts with greater force than before, ejecting a greater SV. By increasing contractility in this fashion, SV and cardiac output are not compromised by increased afterload in a healthy heart.

As expected, cardiac output increases and decreases with similar changes in HR. However, this relationship is maintained only up to approximately 160 to 180 beats/min in a healthy heart. At higher HRs, there is not enough time for the ventricles to fill completely between each heart beat. An excessive HR causes a decrease in EDV, a decrease in SV, and a decrease in cardiac output. The decrease in EDV associated with an elevated HR usually occurs at significantly less than 160 beats/min in the failing heart.

 Rule of Thumb

Increase in HR increases cardiac output in a healthy heart up to a rate of 160 to 180 beats/min.

The combined effects of preload, afterload, contractility, and HR on cardiac performance are graphically portrayed in Figure 9-10. The middle ventricular function curve represents the normal state. The upper, steeper curve represents a hyperdynamic heart. In the hyperdynamic heart, a given preload results in a greater than normal cardiac output. Factors contributing to this state include decreased afterload, increased contractility (decreased ESV), and increased HR. The bottom curve has less slope than normal, indicating a hypodynamic heart. Factors contributing to this state include increased afterload, decreased contractility (increased ESV), and decreased rate. When the pumping efficiency of the heart is so low that cardiac output is inadequate to meet tissues needs, the heart is said to be in congestive heart failure.

Cardiovascular Control Mechanisms

Cardiovascular control is achieved by integrating local and central regulatory mechanisms that affect both the heart and the vasculature. The goal is to ensure that all tissues receive sufficient blood flow to meet their metabolic needs. Under normal resting conditions, this goal is achieved mostly by local regulation of the heart and vasculature. However, when demands are increased or abnormal, such as during exercise or massive bleeding, central mechanisms take over primary control.

 Rule of Thumb

Blood flow to a specific vascular bed is primarily regulated by local mechanisms.

Central control of cardiovascular function occurs by interaction between the brainstem and selected peripheral receptors (Figure 9-11). The brainstem constantly receives feedback from these receptors about the pressure, volume, and chemical status of the blood. The brainstem also receives input from higher brain centers, such as the hypothalamus and cerebral cortex. All these inputs are integrated with the inputs coming from the heart and blood vessels to maintain adequate blood flow and pressure under all but the most abnormal conditions.

Mini Clini

Heart Rate and the Administration of Bronchodilator Drugs

 Problem

You are giving a bronchodilator aerosolized drug to a patient, and you notice a significant increase in the patient’s HR. Would you expect increased HR to be a common side effect of drugs that cause bronchodilation?

Discussion

The discharge rate of the sinus node and the HR are increased by sympathetic nervous stimulation and decreased by parasympathetic nervous stimulation. The airways of the lung are dilated by sympathetic nervous stimulation and constricted by parasympathetic stimulation. Drugs that cause bronchodilation either mimic sympathetic stimulation (sympathomimetic) or block parasympathetic stimulation (parasympatholytic). Both of these drug actions also cause the HR to increase. Parasympatholytic drugs bring about effects similar to sympathetic stimulation because by inhibiting parasympathetic activity, they allow sympathetic impulses to predominate, ultimately causing a sympathetic-like response.

Cardiovascular Control Centers

Figure 9-11 is a simplified diagram of the cardiovascular regulatory centers. Areas in the medulla receive input from higher brain centers, peripheral pressure, and chemical receptors. Stimulation of the vasoconstrictor area within the medulla causes vasoconstriction and increased vascular resistance. A vasodepressor area works mainly by inhibiting the vasoconstrictor center.

Closely associated with the vasoconstrictor center is a cardioaccelerator area. Stimulation of this center increases HR by increasing sympathetic discharge to the sinoatrial and atrioventricular nodes of the heart. A cardioinhibitory area plays the opposite role. Stimulation of this center decreases HR by increasing vagal (parasympathetic) stimulation to the heart.

Higher brain centers also influence the cardiovascular system, both directly and through the medulla. Signals coming from the cerebral cortex in response to exercise, pain, or anxiety pass directly through the cholinergic fibers to the vascular smooth muscle, causing vasodilation. Signals from the hypothalamus, in particular, its heat-regulating areas, indirectly affect HR and vasomotor tone through the cardiovascular centers.

The cardiovascular centers also are affected by local chemical changes in the surrounding blood and cerebrospinal fluid. Decreased levels of CO₂ tend to inhibit the medullary centers. General inhibition of these centers causes a decrease in vascular tone and a decrease in blood pressure. A local decrease in O₂ tension has the opposite effect. Mild hypoxia in this area increases sympathetic discharge rates; this tends to elevate both HR and blood pressure. Severe hypoxia has a depressant effect.

Peripheral Receptors

In addition to high-level and local input, the cardiovascular centers receive signals from peripheral receptors (see Figure 9-11). There are two types of peripheral cardiovascular receptors: baroreceptors, or stretch receptors, and chemoreceptors. Baroreceptors respond to pressure changes, whereas chemoreceptors respond to changes in blood chemistry.

The cardiovascular system has two different sets of baroreceptors. The first set is located in the aortic arch and carotid sinuses. These receptors monitor arterial pressures generated by the left ventricle. The second set is located in the walls of the atria and the large thoracic and pulmonary veins. These low-pressure sensors respond mainly to changes in vascular volumes. Baroreceptor output is directly proportional to the stretch on the vessel wall. The greater the blood pressure, the greater the stretch and the higher the rate of neural discharge to the cardiovascular centers in the medulla.

Together with the cardiovascular regulatory centers, these receptors form a negative feedback loop. In a negative feedback loop, stimulation of a receptor causes an opposite response by the effector. In the case of the arterial receptors, an increase in blood pressure increases aortic and carotid receptor stretch and the discharge rate. The increased discharge rate causes an opposite response by the medullary centers (i.e., depressor response). Decreased blood pressure (decreased baroreceptor output) has the opposite effect, causing peripheral vessel constriction and increased HR and contractility. This mechanism usually restores blood pressure to normal.

Although the high-pressure arterial receptors constantly control blood pressure, the low-pressure sensors are responsible for long-term regulation of plasma volume. The low-pressure atrial and venous baroreceptors regulate plasma volume mainly by activating several chemical and hormonal mechanisms. Table 9-2 provides a detailed description of some of these mechanisms.

TABLE 9-2

Hormonal Control Mechanisms Affecting Blood Pressure

Hormone	Place of Action	Effect
Angiotensin II	Arterioles	↑ SVR (vasoconstriction)
Antidiuretic hormone	Kidneys	↑ Blood volume (↑ water retention)
	Arterioles	↑ SVR (vasoconstriction)
Atrial natriuretic peptide	Arterioles	↓ SVR (vasodilation)
Aldosterone	Kidneys	↑ Blood volume (↑ water and salt retention)
Cortisol	Kidneys	↑ Blood volume (↑ water and salt retention)
Norepinephrine	Heart (beta-1 receptors)	↑ Cardiac output (HR and contractility)
	Arterioles (alpha receptors)	↑ SVR (vasoconstriction)

The major pathways for plasma volume control are outlined in Figure 9-12. Combined with a central nervous system–mediated increase in renal filtration, these humoral mechanisms decrease the overall plasma volume. A decrease in blood volume has the opposite effect (i.e., sodium and water retention and an increase in plasma volume).

Chemoreceptors are small, highly vascularized tissues located near the high-pressure sensors in the aortic arch and carotid sinus. Baroreceptors respond to pressure changes, whereas chemoreceptors are sensitive to changes in blood chemistry. They are strongly stimulated by decreased O₂ tensions, although low pH or high levels of CO₂ also can increase their discharge rate. It is important for the RT to know that the major cardiovascular effects of chemoreceptor stimulation are vasoconstriction and increased HR.

Because these changes occur only when the cardiopulmonary system is overtaxed, the chemoreceptors probably have little influence under normal conditions. However, their influence on respiration is clinically important. For this reason, the peripheral chemoreceptors are discussed in greater detail in Chapter 8.

Response to Changes in Overall Volume

The coordinated response of the cardiovascular system is best shown under abnormal conditions. Among the most common clinical conditions in which all essential regulatory mechanisms come into play is the large blood loss that occurs with hemorrhage. Figure 9-13 illustrates changes in these key factors during progressive blood loss in an animal model.

With 10% blood loss, the immediate decline in the CVP causes a 50% decrease in the discharge rate of the low-pressure (atrial) baroreceptors. There is little change in the activity of the high-pressure (arterial) receptors. The initial response, mediated through the medullary centers, is an increase in sympathetic discharge to the sinus node; this causes a progressive increase in HR. At the same time, plasma levels of antidiuretic hormone (vasopressin) begin to increase. These two initial changes are sufficient to maintain normal arterial blood pressure.

As the blood loss becomes more severe (20%), atrial receptor activity decreases further; this increases the intensity of sympathetic discharge from the cardiovascular centers. Plasma antidiuretic hormone and HR continue to increase, as does peripheral vasculature tone. An increase in vascular tone occurs through constriction of the capacitance vessels in the venous system, slowing the decrease in CVP.

The arterial pressure does not start to decrease until blood loss approaches 30%. At this point, arterial receptor activity begins to decrease, resulting in a marked increase in systemic vascular tone. Despite the magnitude of blood loss, CVP levels off. As long as no further hemorrhage occurs, blood pressure and tissue perfusion can be maintained at adequate levels.

If blood loss continues, central control mechanisms begin to take over. Massive vasoconstriction occurs in the resistance vessels, shunting blood away from skeletal muscle to maintain blood flow to the brain and heart. Increasing levels of local metabolites in these areas, especially CO₂ and other acids, override central control and cause further vessel dilation and increased blood flow. As these metabolites build up and as the tissues become hypoxic, cardiac function becomes impaired, and vasodilation occurs throughout the body. This vasodilation signals the onset of a state of irreversible shock, after which death ensues.

Events of the Cardiac Cycle

This chapter has focused on the mechanical properties of the heart, and the electrical activities of the heart are discussed in Chapter 17. Although they are discussed separately, the mechanical and electrical events are interdependent. Given the crucial role of RTs in dealing with cardiovascular problems, an in-depth knowledge of how these events relate is essential.

The events of the cardiac cycle are depicted in Figure 9-14. The top of the figure shows a time axis scaled in tenths of a second. Next are the timing bars for ventricular systole and diastole and pressure events in the atria, ventricles, and aorta. These are followed by an electrocardiogram (ECG), heart sounds, and ventricular flow (see Chapter 17 for an explanation of the ECG waves).

Going from left to right, the P wave (atrial depolarization) begins the ECG. Earlier, the ventricles have been passively filling with blood through the open atrioventricular valves. Within 0.1 second, the atria contract, causing a slight increase in both atrial and ventricular pressures (the a waves). This atrial contraction helps preload the ventricles, increasing their volume by 25%. This help from the atria to ventricular filling is called the atrial kick. Toward the end of diastole, the electrical impulses from the atria reach the atrioventricular node and bundle branches, and ventricular depolarization (the QRS complex) is initiated. Within a few hundredths of a second after depolarization, the ventricles begin to contract. As soon as ventricular pressures exceed pressures in the atria, the atrioventricular valves close. Closure of the mitral valve occurs first, followed immediately by closure of the tricuspid valve. This closure marks the end of ventricular diastole, producing the first heart sound on the phonocardiogram.

Immediately after atrioventricular valve closure, the ventricles become closed chambers. During this short isovolemic phase of contraction, ventricular pressures increase rapidly. Upward bulging of the atrioventricular valves during this phase causes a slight upswing in atrial pressure graphs, called the c wave. Within 0.05 second, ventricular pressures increase to exceed the pressures in the aorta and pulmonary artery opening the semilunar valves.

Toward the end of systole, as repolarization starts (indicated by the T wave), the ventricles begin to relax. Consequently, ventricular pressures decrease rapidly. When arterial pressures exceed pressures in the relaxing ventricles, the semilunar valves shut. Closure of the semilunar valves generates the second heart sound.

Rather than immediately dropping off, aortic and pulmonary pressures increase again after the semilunar valves close. The dicrotic notch is caused by the elastic recoil of the arteries. This recoil provides the extra “push” that helps maintain the head of pressure created by the ventricles.

As the ventricles continue to relax, their pressures decrease to less than the pressures in the atria. This decline in pressure reopens the atrioventricular valves. As soon as the atrioventricular valves open, the blood collected in the atria rushes to fill the ventricles, causing a rapid decrease in atrial pressures (the v wave). Thereafter, ventricular filling slows as the heart prepares for a new cycle.

Knowledge of these normal events helps one understand many of the diagnostic and monitoring procedures used for patients with cardiopulmonary disorders. Among the most common are the measurement of CVP, balloon-directed pulmonary artery catheterization, and direct arterial pressure monitoring.