STRUCTURE AND FUNCTION OF THE CARDIOVASCULAR AND LYMPHATIC SYSTEMS

Heart Wall

The heart wall has three layers—the pericardium, myocardium, and endocardium. The pericardium is a double-walled membranous sac that encloses the heart (Figure 29-2). The pericardium has several functions. It (1) prevents displacement of the heart during gravitational acceleration or deceleration, (2) is a physical barrier that protects the heart against infection and inflammation from the lungs and pleural space, and (3) contains pain receptors and mechanoreceptors that can elicit reflex changes in blood pressure and heart rate. The outer layer of the pericardium, the parietal pericardium, is composed of a surface layer of mesothelium over a thin layer of connective tissue. The visceral pericardium, or epicardium, is the inner layer of the pericardium. At one point the visceral pericardium folds back and becomes continuous with the parietal pericardium, allowing the large vessels to enter and leave the heart without breaching the pericardial layers.

The visceral and parietal pericardia are separated by a fluid-containing space called the pericardial cavity. The pericardial fluid (10 to 30 ml), which is secreted by cells of the mesothelium, lubricates the membranes that line the pericardial cavity, enabling them to slide over one another with a minimum of friction as the heart beats. The amount and character of the pericardial fluid are altered by inflammation of the pericardium (see Chapter 30).

The thickest layer of the heart wall, the myocardium, is composed of cardiac muscle and is anchored to the heart’s fibrous skeleton. The thickness of the myocardium varies tremendously from one heart chamber to another. Thickness is related to the amount of resistance the muscle must overcome to pump blood from the different chambers. The internal lining of the myocardium is composed of connective tissue and a layer of squamous cells called the endocardium (see Figure 29-2). The endocardial lining of the heart is continuous with the endothelium that lines all the arteries, veins, and capillaries of the body, creating a continuous, closed circulatory system.

Chambers of the Heart

The heart has four chambers: the right atrium, left atrium, right ventricle, and left ventricle. (Blood flow through these chambers is illustrated in Figure 29-3.) The atria are smaller than the ventricles and have thinner walls. The wall of the right atrium is about 2 mm thick, and the wall of the left atrium is about 3 to 5 mm thick. The ventricles have a thicker myocardial layer and make up much of the bulk of the heart. The wall of the right ventricle is about 3 to 5 mm thick, and that of the left ventricle, the most muscular chamber, is about 13 to 15 mm. The ventricles are formed by a continuum of muscle fibers that take origin from the fibrous skeleton at the base of the heart (chiefly around the aortic orifice).

The myocardial thickness of each cardiac chamber depends on the amount of pressure or resistance it must overcome to eject blood. The two atria have the thinnest walls because they are low-pressure chambers that serve as storage units and conduits for blood that is emptied into the ventricles. Normally, there is little resistance to flow from the atria to the ventricles. The ventricles, on the other hand, must propel blood all the way through the pulmonary or systemic circulation. The ventricular myocardium also must be strong enough to pump against pressures in the pulmonary or systemic vessels. The mean pulmonary capillary pressure, which is the major force favoring movement of fluid out of the pulmonary capillaries into the interstitium, is only 15 mmHg. By comparison, the mean arterial pressure is about 92 mmHg. Pressure is greatest in the systemic circulation, driven by the left ventricle; the left ventricle’s myocardium is several times thicker than that of the right ventricle.

The right ventricle is shaped like a crescent, or triangle, enabling it to function like a bellows and efficiently eject large volumes of blood through a very small valve into the low-pressure pulmonary system. The left ventricle is larger and bullet shaped, helping it to eject blood through a relatively large valve opening into the high-pressure systemic circulation.

The ventricles are structurally more complex than the atria. Each ventricle contains muscle fibers that divide it roughly into an inflow tract, which receives blood from the atrium, and an outflow tract, which sends blood to the circulation (see Figure 29-3).

Normally blood does not flow between the chambers of the right side of the heart and the chambers of the left side of the heart. The adult right and left sides of the heart are separated by an intact septal membrane. The atria are separated by the interatrial septum, and the ventricles by the interventricular septum. The interventricular septum is an extension of the fibrous skeleton of the heart. Indentations of the endocardium form valves that separate the atria from the ventricles and the ventricles from the aorta and pulmonary arteries.

Fibrous Skeleton of the Heart

Four rings of dense fibrous connective tissue provide a firm anchorage for the attachments of the atrial and ventricular musculature, as well as the valvular tissue. The fibrous rings are adjacent and form a central, fibrous supporting structure collectively termed the anuli fibrosi cordis.

Valves of the Heart

One-way blood flow through the heart is ensured by the four heart valves. During ventricular relaxation the two atrioventricular valves open and blood flows from the higher-pressure atria to the relaxed ventricles. With increasing ventricular pressure these valves close and prevent backflow into the atria as the ventricles contract. The semilunar valves of the heart open when intraventricular pressure exceeds aortic and pulmonary pressures and blood flows out of the ventricles and into the pulmonary and systemic circulations. After ventricular contraction and ejection, intraventricular pressure falls and the pulmonic and aortic semilunar valves close, preventing backflow into the right and left ventricles (Figure 29-4; see also Figure 29-3).

The atrioventricular (AV) (tricuspid and mitral) valve openings are guarded by flaps of tissue called leaflets or cusps that are attached to the papillary muscles by the chordae tendineae (see Figure 29-3). The papillary muscles are extensions of the myocardium that pull the cusps together and downward at the onset of ventricular contraction, thus preventing their backward expulsion into the atria (see p. 1096 for a description of pressure changes and valvular function).

The right AV valve is called the tricuspid valve because it has three cusps. The tricuspid opening (orifice) has the largest diameter of all the heart valves. The left AV valve is a bicuspid (two cusps) valve called the mitral valve. The mitral valve resembles a cone-shaped funnel that extends into the cusps, which are connected by a fibrous tissue called the commissure. The anterior cusp of the mitral valve is continuous with supporting tissues of the aortic semilunar valve cusps and the left coronary valve cusps. (The coronary circulation is described on p. 1096.) Thus damage to this continuous tissue can alter function of the aortic as well as the mitral valves.

The tricuspid and mitral valves function as a unit because the atrium, fibrous rings, valvular tissue, chordae tendineae, papillary muscles, and ventricular walls are connected. Collectively, these six structures are known as the mitral and tricuspid complex. Damage to any one of the complex’s six components can alter function significantly.

Blood leaves the right ventricle through the pulmonic semilunar valve, and it leaves the left ventricle through the aortic semilunar valve (see Figures 29-3 and 29-4). The pulmonic and aortic semilunar valves have three cup-shaped cusps that arise from the fibrous skeleton. The pulmonic cusps are slightly thinner than the aortic cusps. The lower edges of each cusp are suspended from the root of the pulmonary artery or aorta, with the upper valve edges freely projecting into the vessel lumen. When the ventricles contract, the cusps behave like one-way swinging doors. The force of the blood propels the cusps outward against the vessel wall. When the ventricles relax, blood fills the cusps and causes their free edges to meet in the middle of the vessel, closing the valve and preventing any backflow.

Great Vessels

Blood moves in and out of the heart through several large vessels (see Figure 29-3). The right heart receives venous blood from the systemic circulation through the superior vena cava and the inferior vena cava, which enter the right atrium. Blood leaves the right ventricle and enters the pulmonary circulation through the pulmonary artery. The pulmonary artery divides into right and left pulmonary arteries to transport unoxygenated blood from the right heart to the right and left lungs. The pulmonary arteries branch further into the pulmonary capillary bed, where oxygen and carbon dioxide exchange occurs.

The four pulmonary veins, two from the right lung and two from the left lung, carry oxygenated blood from the lungs to the left side of the heart. The oxygenated blood moves through the left atrium and ventricle and out into the aorta, which delivers it to systemic vessels that supply the body.

Blood Flow During the Cardiac Cycle

The pumping action of the heart consists of contraction and relaxation of the myocardial layer of the heart wall. Each ventricular contraction and the relaxation that follows it constitute one cardiac cycle. (Blood flow through the heart during a single cardiac cycle is illustrated in Figure 29-5.) During relaxation, termed diastole, blood fills the ventricles. The contraction that follows, termed systole, propels the blood out of the ventricles and into the circulation. Contraction of the left ventricle is slightly earlier than contraction of the right ventricle.

During ventricular systole, blood from the veins of the systemic circulation enters the thin-walled right atrium from the superior vena cava and the inferior vena cava (see Figures 29-3 and 29-5). Venous blood from the coronary circulation enters the right atrium through the coronary sinus. The right atrium fills and distends, pushing open the right AV (tricuspid) valve. This permits blood to fill the right ventricle during ventricular diastole (sometimes called atrial systole). The same sequence of events occurs a split second earlier in the left heart. The four pulmonary veins, two from the right lung and two from the left lung, carry blood from the pulmonary circulation to the left atrium. As the left atrium fills, it pushes the cusps of the mitral valve open and blood flows into the left ventricle. Left atrial contraction, “atrial kick,” provides a significant increase of blood to the left ventricle. Filling of the right and left ventricles occurs during one period of diastole.

Five phases of the cardiac cycle can be identified (Figures 29-6 and 29-7):

As blood is pushed through the inflow and outflow tracts of the ventricles, it flows around the crista supraventricularis—the muscle that separates the inflow from the outflow tracts—and is mixed by passing through the strands of the trabeculae carneae.

Normal Intracardiac Pressures

Normal intracardiac pressures are shown in Table 29-1 and Figures 29-6 and 29-8. Atrial pressure curves are composed of the a wave, which is generated by atrial contraction, and the v wave, which is an early diastolic peak caused by filling of the atrium from the peripheral veins. The x descent follows the a wave and is produced because of descent of the tricuspid valve ring and by the ejection of blood from both ventricles. The y descent follows the v wave and reflects the rapid flow of blood from the great veins and right atrium into the right ventricle. A small deflection, the c wave, occurs after the a wave in early systole and may represent bulging of the mitral valve into the left atrium during early systole. Ventricular pressures are illustrated by a peak systolic pressure and an end-diastolic pressure, which is the ventricular pressure immediately before the onset of systole. The minimal left ventricular pressure occurs in early diastole.

Coronary Arteries

The major coronary arteries are the right coronary artery (RCA) and the left coronary artery (LCA) (see Figure 29-9). These arteries traverse the epicardium and branch several times. The right coronary artery has greater flow than the left in 50% of individuals, the left greater than the right in 20%, and equal flow in each in 30%.¹ The pattern of branching through the visceral pericardium differs from heart to heart. The branches enter the myocardium and endocardium and branch further to become arterioles and then capillaries. Although the coronary arteries are smaller in women than men, this is attributable to differences in heart weight.

The left coronary artery arises from a single ostium (opening) behind the left cusp of the aortic semilunar valve. This artery ranges from a few millimeters to a few centimeters in length. It passes between the left atrial appendage and the pulmonary artery and generally divides into two branches—the left anterior descending artery and the circumflex artery. Other branches of the left main coronary artery are distributed diagonally across the free wall of the left ventricle.

The left anterior descending artery (LAD), also called the anterior interventricular artery, delivers blood to portions of the left and right ventricles and much of the interventricular septum. The left anterior descending artery travels down the anterior surface of the interventricular septum toward the apex of the heart.

The circumflex artery travels in a groove called the coronary sulcus, which separates the left atrium from the left ventricle, to the left border of the heart. It supplies blood to the left atrium and the lateral wall of the left ventricle. The circumflex artery often branches to the posterior surfaces of the left atrium and left ventricle (see Figure 29-9).

The right coronary artery originates from an ostium behind the right aortic cusp, travels behind the pulmonary artery, and extends around the right heart to the heart’s posterior surface, where it branches to the atrium and the ventricle. The three major branches of the right coronary artery include the conus, which supplies blood to the upper right ventricle; the right marginal branch, which traverses the right ventricle to the apex; and the posterior descending branch, which lies in the posterior interventricular sulcus and supplies smaller branches to both ventricles.

Collateral Arteries

The collateral arteries are really connections, or anastomoses, between two branches of the same coronary artery or connections of branches of the right coronary artery with branches of the left. They are particularly common within the interventricular and interatrial septa, at the apex of the heart, over the anterior surface of the right ventricle, and around the sinus node. The epicardium contains more collateral vessels than the endocardium.

The functional importance of the collateral circulation is that it protects the heart from ischemia. The collateral circulation is responsible for supplying blood and oxygen to the myocardium that has been deprived of oxygen following narrowing of a major coronary artery (coronary artery disease). Gradual coronary occlusion results in the growth of coronary collaterals. New collateral vessels are formed through two processes, arteriogenesis (new artery growth from preexisting arteries) and angiogenesis (growth of new capillaries within a tissue).²

The stimulus to collateral arteriogenesis is the shear stress caused by increased blood flow velocity that occurs close to the site of occlusion. Shear stress activates the endothelium of the preexisting arterioles and stimulates the production of growth factors and cytokines, including monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF).³ Monocytes/macrophages are called to the area of endothelial activation and release more growth factors and cytokines. Recent studies suggest that adequate monocyte numbers and function are critical to the growth of collaterals in individuals with coronary artery disease.³ As the collaterals begin to accept coronary flow, flow stress and pressure changes cause them to be restructured and remodeled.

Angiogenesis also is stimulated by numerous growth factors (VEGF, fibroblast growth factor [FGF]) and through the production of nitric oxide.^2,4 Unfortunately, diabetes, which predisposes to coronary artery disease, also impedes collateral formation because of increased production of antiangiogenic factors such as endostatin and angiostatin.⁵ The presence of an effective collateral system has been shown to be protective in coronary artery disease, and an increased understanding of these processes has led to the use of angiogenic factors in the treatment of coronary artery disease that is not responsive to more conventional therapies.⁶

Coronary Capillaries

The heart has an extensive capillary network, with approximately 3300 capillaries per square millimeter (ca/mm²) or about one capillary per muscle cell (muscle fiber). Blood travels from the arteries to the arterioles and then into the capillaries, where exchange of oxygen and other nutrients takes place.

Alterations of the cardiac muscles dramatically affect blood flow in the capillaries. For example, in ventricular hypertrophy (enlargement of the ventricular myocardium), the capillary network does not expand along with muscle fiber size. Therefore, the same number of capillaries must now perfuse a larger area. This results in decreased exchange of oxygen and nutrients. At rest, the heart extracts 70% to 80% of the oxygen delivered to it and coronary blood flow is directly correlated with myocardial oxygen consumption.¹

Coronary Veins and Lymphatic Vessels

After passing through the extensive capillary network, blood from the coronary arteries drains into the cardiac veins, which travel alongside the arteries. Most of the venous drainage of the heart occurs through veins in the visceral pericardium. The veins then feed into the great cardiac vein (see Figure 29-9) and coronary sinus on the posterior surface of the heart, between the atria and ventricles, in the coronary sulcus. Venous coronary blood empties into the right atrium from the coronary sinus. Blood from the left ventricular walls generally is drained through the coronary sinus and its tributaries, which together form the largest system of coronary veins. The great cardiac vein primarily drains the anterior surface of the heart. The posterior vein of the left ventricle, the largest on the posterior surface of the heart, branches from the coronary sinus and accompanies the circumflex artery.

The myocardium has an extensive system of lymphatic vessels. With cardiac contraction the lymphatic vessels drain fluid to lymph nodes in the anterior mediastinum that eventually empty into the superior vena cava. The lymphatics are important for protecting the myocardium against injury. (The lymphatic vessels are described on p. 1131.)

Conduction System

Normally electrical impulses arise in the sinoatrial (SA) node (SA node, sinus node), which is often called the pacemaker of the heart. The SA node is located at the junction of the right atrium and superior vena cava, just above the tricuspid valve (see Figure 29-10). The SA node lies only 1 mm or less beneath the visceral pericardium, making it vulnerable to injury and disease, especially pericardial inflammation. The SA node is nourished by the sinus node artery, which passes through the center of the node. Numerous autonomic nerve endings are within the node. The SA node is heavily innervated by both sympathetic and parasympathetic nerve fibers.⁷ The SA node’s P cells, so-called because they are pale and primitive appearing, are assumed to be the site of impulse formation.

In the resting adult the SA node generates about 75 action potentials per minute. Each one travels rapidly from cell to cell and through special pathways in the atrial myocardium, causing both atria to contract, beginning systole. Ventricular contraction is delayed because the fibrous skeleton of the heart interrupts cell-to-cell transmission of the electrical impulses. The action potential is transmitted from the atrial to the ventricular myocardium through fibers of the conduction system, traveling first to the atrioventricular (AV) node then to the bundle of His (atrioventricular bundle, common bundle), and finally through the bundle branches of the interventricular septum to Purkinje fibers in the heart wall (see Figure 29-10).

The AV node is well situated for mediating conduction between the atria and ventricles. It is located in the right atrial wall above the tricuspid valve and anterior to the ostium of the coronary sinus. There is much variation from one heart to another in the size and length of the AV node fibers. Generally the AV node is thicker and shorter and has fewer P cells than the SA node. Behind the AV node are numerous autonomic parasympathetic ganglia. (The nervous systems are described in Chapter 14.) These ganglia may serve as receptors for the vagus nerve and cause slowing of impulse conduction through the AV node.¹

Conducting fibers from the AV node converge to form the bundle of His. The bundle of His, which is triangular shaped, lies within the posterior border of the interventricular septum. The two lower ends of the triangle give rise to the right and left bundle branches. The right bundle branch (RBB) is thin and travels without much branching to the right ventricular apex. Because of its thinness and relative lack of branches, the RBB is susceptible to interruption by damage to the endocardium.

The left bundle branch (LBB) arises perpendicularly from the bundle of His and, in some hearts, divides into two branches, or fascicles. The left anterior bundle branch (LABB) passes the left anterior papillary muscle and the base of the left ventricle and crosses the aortic outflow tract. Damage to the aortic valve or the left ventricle can interrupt this branch. The left posterior bundle branch (LPBB) travels posteriorly, crossing the left ventricular inflow tract to the base of the left posterior papillary muscle. This branch spreads diffusely through the posterior inferior left ventricular wall. Blood flow through this portion of the left ventricle is relatively nonturbulent, so the LPBB is somewhat protected from injury caused by wear and tear. The Purkinje fibers are the terminal branches of the right and left bundle branches. They extend from the ventricular apices to the fibrous rings and penetrate the heart wall to the outer myocardium. P cells are found also among the Purkinje fibers.

Cardiac Innervation

Although the heart’s nodes and conduction system generate cardiac action potentials independently, the autonomic nervous system influences the rate of impulse generation (firing), depolarization, and repolarization of the myocardium and the strength of atrial and ventricular contraction. Autonomic neural transmission produces changes in the heart and circulatory system faster than metabolic or humoral agents (see Figure 29-11). Speed is important, for example, in stimulating the heart to increase its pumping action during times of stress or fear, the so-called fight-or-flight response. Although increased delivery of oxygen, glucose, hormones, and other blood-borne factors sustains increased cardiac activity, the rapid initiation of increased activity depends on the sympathetic and parasympathetic fibers of the autonomic nervous system. (The autonomic nervous system is described and illustrated in Chapter 14.)

Myocardial Cells

The cells of cardiac muscle (the myocardium) and of skeletal muscle are nearly identical in structure, function, and microscopic appearance. (The properties of skeletal muscle are described in detail in Chapter 41.) Both types of muscle tissue are composed of long, narrow cells, called fibers, that contain basically the same structures: bundles of longitudinally arranged myofibrils; a nucleus (cardiac muscle) or many nuclei (skeletal muscle); mitochondria; an internal membrane system (the sarcoplasmic reticulum); cytoplasm (sarcoplasm); and a plasma membrane (the sarcolemma), which encloses the cell. Cardiac and skeletal muscle cells also have an “external” membrane system made up of transverse tubules (T tubules) formed by invaginations of the sarcolemma. The sarcoplasmic reticulum forms a network of channels that surround the muscle fiber.

The microscopic appearance of cardiac and skeletal muscle is somewhat similar as well (see Chapter 1, Table 1-8). Because the myofibrils in both types of fibers are made up of alternating light and dark bands of protein, the fibers appear striped, or striated. The dark and light bands of the myofibrils make up longitudinal repeating units called sarcomeres. The length of the sarcomeres, normally between 1.6 and 2.2 mm, is important because it determines the limits of myocardial stretch at the end of diastole and subsequently the force of contraction during systole.

Cardiac muscle differs from skeletal muscle in several respects that reflect heart function. Cardiac cells are arranged in branching networks throughout the myocardium, whereas skeletal muscle cells tend to be arranged in parallel throughout the length of the muscle. Cardiac fibers have only one nucleus, whereas skeletal muscle cells have many nuclei. Other differences enable cardiac fibers to (1) transmit action potentials quickly from cell to cell, (2) maintain high levels of energy synthesis, and (3) gain access to more ions, particularly sodium and potassium, in the extracellular environment.

Rapid transmission of electrical impulses from cardiac fiber to cardiac fiber is possible because the network of fibers is connected at specialized intercellular junctions called intercalated disks. Intercalated disks are thickened portions of the sarcolemma that enable electrical impulses to spread quickly in a continuous cell-to-cell (syncytial) fashion. The intercalated disks contain two junctions: desmosomes, which attach one cell to another; and gap junctions, which allow the electrical impulse to spread from cell to cell (see Chapter 1). Together these junctions provide a low-resistance pathway for impulse propagation.

Unlike skeletal muscle, the heart cannot rest and is in constant need of energy compounds, such as adenosine triphosphate (ATP). Therefore, the cytoplasm surrounding the bundles of myofibrils in each cardiac muscle cell contains a superabundance of mitochondria (25% of the cellular volume). Cardiac muscle cells have more mitochondria than skeletal muscle cells. The large numbers of mitochondria provide the necessary respiratory enzymes for aerobic metabolism and supply quantities of ATP sufficient for the constant action of the myocardium.

The third major difference between cardiac and skeletal muscle cells has to do with the T tubule system. Cardiac fibers contain more T tubules than skeletal muscle fibers. This gives each myofibril in the myocardium ready access to molecules it needs for the continuous transmission of action potentials, a process that involves transport of sodium and potassium through the walls of the T tubules. (The mechanisms by which sodium and potassium transport causes transmission of cardiac action potentials are described in Chapters 1 and 41.) Because the T tubule system is continuous with the extracellular space and the interstitial fluid, it facilitates the rapid transmission of electrical impulses from the surface of the sarcolemma to the myofibrils inside the fiber. This activates all the myofibrils of one fiber simultaneously. The sarcoplasmic reticulum is located around the myofibrils. When an action potential is transmitted through the T tubules, it induces the sarcoplasmic reticulum to release its stored calcium, which activates the contractile proteins, actin and myosin.

Myocardial Contraction and Relaxation

Myocardial contractility is a change in developed tension at a given resting fiber length. In functional terms, contractility is the ability of the heart muscle to shorten. On a molecular basis, thin filaments of actin slide over thick filaments of myosin, called the cross-bridge theory of muscle contraction. Anatomically, contraction occurs when the sarcomere shortens, causing adjacent Z lines to move closer together (Figure 29-18). The width of the A band, which contains the thick myosin filaments, is unchanged. The movement comes from the long sets of filaments. The degree of shortening of the muscle fibers depends on how much the thin filaments overlap the thick filaments. Maximal contraction occurs when the sarcomere length is 2.2 mm. At 2.2 mm the number of cross-bridge attachments between actin and myosin is maximal.

Frank-Starling Law of the Heart

Cardiac muscle, like other muscle, increases its strength of contraction when it is stretched. This relationship was described in 1914 by a British physiologist, Ernest Starling, who based his studies on the earlier work of a German physiologist, Otto Frank. In 1914 Starling wrote that “the output of any heart can be varied within wide limits by alterations of the venous inflow, and that within these limits it varies directly as the venous inflow. So long as the functional condition of the heart remains constant, the amount put out at each beat depends directly on the diastolic filling.”^12a

The Frank-Starling law of the heart, or the length-tension relationship of cardiac muscle, relates resting sarcomere length, expressed as the volume of blood in the heart at the end of diastole, or end-diastolic volume, to tension generation, described as development of left ventricular pressure. Thus the volume of blood in the heart at the end of diastole (the length of its muscle fibers) is directly related to the force of contraction during the next systole. Although the change in pressure is related to volume of the ventricle and, consequently, to the length of the ventricular muscle fibers, it is common to use preload (i.e., filling pressure) as an index of ventricular volume. The length-tension mechanism is the major mechanism by which the normal right and left ventricles maintain equal minute outputs even though their stroke outputs may vary considerably during normal respiration. For example, changes in volume occur when an individual assumes a reclining position after being in a standing position; the volume of blood returning to the heart temporarily increases. The right ventricle stretches to accommodate this increase in volume and thereby increases its force of contraction. A larger stroke volume (i.e., the amount of blood ejected per beat) is pumped to the lungs, generating higher pressures. Pulmonary vascular pressure increases, causing a rise in the left ventricular filling pressure or preload. Left ventricular volume and pressure increase. The left ventricle pumps a larger stroke volume, and arterial vascular pressure rises.

The mechanical function of the heart is characterized by a number of length-tension curves (Figure 29-20). Factors that increase contractility (i.e., positive inotropic), such as sympathetic nerve stimulation, cause the heart to operate on a higher length-tension curve (curve A in Figure 29-20). A higher tension or increase in ventricular stroke volume is generated without a necessary change in left ventricular end-diastolic volume or fiber length. Heart failure (curve C in Figure 29-20) is characterized by a lower length-tension curve (see Chapter 30). The failing or dilated heart may not be able to use the Frank-Starling law of the heart because its fibers are already stretched beyond their optimal length. The failing heart responds to increased filling or stretch with a progressive decline in force of contraction. Thus at the same left ventricular end-diastolic volume as curves A and B (see Figure 29-20), the force of contraction of stroke volume is decreased.

The cross-bridge theory partially accounts for the length-tension mechanism of cardiac muscle. According to the Frank-Starling law, the longer the initial resting length of the cardiac muscle fiber (optimal length is between 2.2 and 2.4 mm), the greater the strength of contraction. At 2.2 mm there is an optimal number of active cross-bridges between actin and myosin. If the fibers are stretched beyond 2.2 to 2.4 mm, the force of contraction decreases because actin and myosin become partially disengaged, disrupting many of the cross-bridges. Excessive stretching, to about 3.65 mm, causes actin and myosin to become completely disengaged and developed tension (force of contraction) to drop to zero. The relationship between stretch and contraction can be compared with that of a rubber band. To a certain point, the more the rubber band is stretched, the farther it will fly when one end is released; beyond that point, however, the rubber band will break.

Laplace’s Law

In Laplace’s law, wall tension is related directly to the product of intraventricular pressure and internal radius and inversely to the wall thickness. This relationship can be calculated by Laplace’s equation:

where T = wall tension, p = intraventricular pressure, r = internal radius of the sphere, and μm = wall thickness. In other words, the amount of tension generated in the wall of the ventricle (or any chamber or vessel) to produce a given intraventricular pressure depends on the size (radius and wall thickness) of the ventricle.

The law of Laplace is useful for understanding aneurysm formation, distensibility in blood vessels, and the effects of ventricular dilation on myocardial contraction. Dilation is an important factor in heart failure (see Chapter 30). With a dilated ventricle, myocardial fibers in the wall must develop greater tension to produce a given pressure within the ventricle. The disadvantage of dilation is that the increased force, or tension, in the myocardial fibers required to develop a given pressure inside a dilated ventricle results in a decrease in the rate of fiber shortening, thereby decreasing the ability of the ventricle to eject blood.

Preload

Left ventricular preload is the pressure generated in the left ventricle at the end of diastole, or left ventricular end-diastolic pressure (LVEDP). It is determined by left ventricular end-diastolic volume (LVEDV), according to the Frank-Starling law, which stretches the cardiac muscle fibers, which in turn develop tension, or force, for contraction. Preload is determined by two primary factors: (1) the amount of venous return to the ventricle and (2) the blood left in the ventricle after systole (end-systolic volume). End-systolic volume is dependent on the strength of ventricular contraction and the resistance to ventricular emptying. Within a physiologic range of muscle stretching (2.2 to 2.4 mm), increased preload increases cardiac output (volume of blood pumped per minute; see Figure 29-19). When preload exceeds the physiologic range, further muscle stretching causes a decline in cardiac output (see Frank-Starling law, p. 1109). In monitoring preload the clinician measures indexes of left ventricular end-diastolic pressure. Pressure changes are important because increased left ventricular filling pressures “back up” into the pulmonary circulation, where they force plasma out through vessel walls, causing fluid to accumulate in lung tissues (pulmonary edema; see Chapter 33). Treatment goals are to maintain an end-diastolic volume and pressure that will maintain or increase cardiac output.

Afterload

Left ventricular afterload is the resistance to ejection of blood from the left ventricle. Aortic systolic pressure is a good index of afterload. Low aortic pressures (decreased afterload) enable the heart to contract more rapidly, whereas high aortic pressures (increased afterload) slow contraction and cause higher workloads against which the heart must function so it can eject less blood. Pressure in the ventricle must exceed aortic pressure before blood can be pumped out during systole. Increased aortic pressure is usually the result of increased peripheral vascular resistance (PVR), also called total peripheral resistance (TPR). In individuals with hypertension, increased PVR means that afterload is chronically elevated resulting in increased ventricular workload and hypertrophy of the myocardium.

Myocardial Contractility

Stroke volume, or the volume of blood ejected during systole, depends on the force of contraction, which depends on myocardial contractility, or the degree of myocardial fiber shortening. Three major factors determine the force of contraction: (1) changes in the stretching of the ventricular myocardium caused by changes in ventricular volume (preload), (2) alterations in the sympathetic activation of the ventricles, and (3) adequacy of myocardial oxygen supply (see Figure 29-19). As discussed, increased blood flow from the veins into the heart distends the ventricle by increasing preload, which, within the physiologic range, increases the stroke volume and, subsequently, cardiac output.

Chemicals affecting contractility are called inotropic agents. The most important positive inotropic agents are epinephrine and norepinephrine released from the sympathetic nervous system. Other positive ionotropes include thyroid hormone and dopamine. The most important negative ionotropic agent is acetylcholine released from the vagus nerve. Many drugs have positive or negative ionotropic properties that can have profound effects on cardiac function.

Myocardial contractility also is affected by oxygen and carbon dioxide levels (tensions) in the coronary blood. With severe hypoxemia (arterial oxygen saturation less than 50%), contractility is decreased. With less severe hypoxemia (saturation more than 50%), contractility is stimulated. Moderate degrees of hypoxemia may increase contractility by enhancing the myocardial response to circulating catecholamines.¹

Preload, afterload, and contractility all interact with one another to determine stroke volume and cardiac output. Changes in any one of these factors can result in deleterious effects on the others, resulting in heart failure (see Chapter 30).

Heart Rate

The average heart rate in healthy adults is about 70 beats/minute. The average heart rate is significantly greater in children. Heart rate diminishes by 10 to 20 beats/minute during sleep and can accelerate to more than 100 beats/minute during muscular activity or emotional excitement. In well-conditioned athletes at rest the heart rate is normally about 50 to 60 beats/minute. In highly trained or elite athletes the resting heart rate can be less than 50 beats/minute. The low resting heart rate is the result of increased vagal stimulation and lower sympathetic stimulation.

Highly trained athletes also have a greater stroke volume and lower peripheral resistance than they had before training. The lowered peripheral resistance is thought to be caused by an increase in the number of arterioles in skeletal muscle. The decrease in peripheral resistance increases the venous return. The slow heart rate (and therefore prolonged diastole) combined with the increased venous return results in a higher end-diastolic ventricular volume.^1,7 The increased end-diastolic fiber length increases stroke volume, which helps compensate for the decreased heart rate so that cardiac output is maintained.

Neural factors, including neural reflexes, and hormonal and chemical factors influence the heart rate. Neural control is exerted by the central and autonomic nervous systems. Hormonal factors include the catecholamines norepinephrine and epinephrine, thyroid hormones, growth hormones, and pancreatic hormones. (Hormonal function is described in Chapter 20. Stimulation by the sympathetic nervous system increases the rhythmicity of the cardiac pacemaker (SA node), whereas the parasympathetic stimulation has an inhibiting effect.

Arterial Vessels

Arterial walls are composed of elastic connective tissue, fibrous connective tissue, and smooth muscle. The two types of arteries are elastic and muscular. The elastic arteries have a very thick tunica media that contains more elastic fibers than smooth muscle fibers. Elastic arteries include the aorta and its major branches and the pulmonary trunk. Elasticity enables the vessel to stretch as blood is ejected from the heart during systole. During diastole, elasticity promotes recoil of the arteries, which is important for maintaining blood pressure within the vessels.

The muscular arteries are the medium-size and small arteries farther from the heart than the elastic arteries. They contain fewer elastic fibers and more muscle fibers than the elastic arteries because, being farther from the heart, they have less need of the properties of stretch and recoil. The function of the muscular arteries is to distribute blood to arterioles throughout the body. They also play a role in controlling blood flow because their smooth muscle can be stimulated to contract or relax. Contraction narrows the vessel lumen (the internal cavity of the vessel), which diminishes flow through the vessel. This condition is termed vasoconstriction. The smooth muscle layer also can be stimulated to relax, which permits more blood to flow through the vessel lumen. This state is called vasodilation.

An artery becomes an arteriole at the point where the diameter of its lumen narrows to less than 0.5 mm. The arterioles are composed almost exclusively of smooth muscle, with little elastic tissue. Arterioles regulate the flow of blood into the capillaries by vasoconstriction, which retards the flow of blood into the capillaries, and vasodilation, which permits blood to enter the capillaries freely (Figure 29-25, p. 1117). The thick, smooth muscle layer of the arterioles is a major determinant of the resistance blood encounters as it flows through the systemic circulation.

The capillary network is composed of connective channels, or thoroughfares, called metarterioles, and “true” capillaries (Figure 29-26, p. 1118). The capillaries branch from the metarterioles, meeting at a ring of smooth muscle called the precapillary sphincters. As the sphincters contract and relax, they regulate blood flow through the capillaries. Appropriately stimulated, the precapillary sphincters help maintain arterial pressure and regulate selective flow to vascular beds.

The capillary walls are very thin, making possible the rapid exchange of substrates, metabolites, and special products (e.g., hormones) between the blood and the interstitial fluid, from which they are taken up by the cells. The capillary wall consists of a single layer of endothelial cells surrounded by the thin basement membrane of the tunica intima. A single endothelial cell may form the entire vessel wall if the capillary has no tunica media or tunica externa. In some capillaries the endothelial cells contain oval windows or pores termed fenestrations. Fenestrations generally are covered by a thin diaphragm.

Substances pass between the capillary lumen and the interstitial fluid in several ways: (1) through junctions between endothelial cells, (2) through fenestrations in endothelial cells, (3) in vesicles moved by active transport across the endothelial cell membrane, or (4) by diffusion through the endothelial cell membrane. (Movement across cell membranes is described in Chapter 1.) A single capillary may be only 0.5 to 1 mm in length and 0.01 mm in diameter, but the capillaries are so numerous that their total surface area may be more than 600 m².

Endothelium

All tissues depend on a blood supply and the blood supply depends on endothelial cells, which form the lining, or endothelium, of the blood vessel (Figure 29-27). Endothelial cells are really quite remarkable in that they can adjust their number and arrangement to accommodate local requirements. Thus they are a life-support tissue extending and remodeling the network of blood vessels to enable tissue growth, promote contraction or relaxation or vasomotion, repair, antithrombogenesis, and fibrinolysis. The endothelium performs these vital functions via synthesis and release of vasoactive chemicals.^18–20 Box 29-1 and Figures 29-28 (p. 1120) and 29-29 (p. 1121) summarize some of the more important functions. Endothelial injury and dysfunction are central processes in many of the most common and serious cardiovascular disorders including hypertension and atherosclerosis (see p. 1157).

Veins

The smallest venules closest to the capillaries have an inner lining composed of the endothelium of the tunica intima and surrounded by fibrous tissue. The largest venules, those farthest from the capillaries, are surrounded by a few smooth muscle fibers comprising a thin tunica media.

Compared with arteries, veins are thin walled and fibrous with a larger diameter (see Figure 29-23). A given vein is larger than the artery that lies within the same sheath. Veins are more numerous than arteries. In veins the tunica externa has less elastic tissue than in arteries, so veins do not recoil after distention as quickly as arteries. Like arteries, veins receive nourishment from the tiny vasa vasorum. Some veins, most commonly in the lower limbs, contain valves that regulate the one-way flow of blood toward the heart (Figure 29-30, p. 1121). These valves are folds of the tunica intima and resemble the semilunar valves of the heart. Backflow in veins of the legs is stopped as the flaps of the valves fill with blood and block the vessel. The position of the valves also facilitates blood flow in the proper direction during venous compression. When a person stands up, contraction of the skeletal muscles of the legs compresses the deep veins of the legs and assists the flow of blood toward the heart. This important mechanism of venous return is called the muscle pump (Figure 29-31, p. 1122).

Pressure and Resistance

Blood flow is determined primarily by two factors: pressure and resistance. Pressure in a liquid system is the force exerted on the liquid per unit area and is expressed as dynes per square centimeter (dynes/cm²), millimeters of mercury (mmHg), or torr. Blood flow depends partly on the difference between pressures in the arterial and venous vessels supplying the organ. Fluid moves from the arterial “side” of the capillaries, a region of greater pressure, to the venous side, a region of lesser pressure.

Resistance is the opposition to force. In the cardiovascular system most opposition to blood flow is provided by the diameter and length of the blood vessels themselves. Therefore changes in blood flow through an organ result from changes in the vascular resistance within the organ. The major mechanisms causing changes in vascular resistance are an increase or a decrease in vessel diameter and the opening or closing of vascular channels. Resistance in a vessel is inversely related to blood flow; that is, increased resistance leads to decreased blood flow.

Blood flow (Q) through a vessel can be calculated from measurements of pressure at the inflow end of the vessel (P₁), pressure at the outflow end of the vessel (P₂), and resistance (R). The difference between P₁ and P₂ often is referred to as the change in pressure and is expressed as δP. The following formula, which expresses Poiseuille’s law, shows the relationship among blood flow, pressure, and resistance:

where Q = blood flow, δP = the pressure difference (P₁ −P₂), and R = resistance.

Resistance to flow cannot be measured directly, but it can be calculated if the pressure difference and flow volumes are known.

Flow varies inversely with the viscosity of the fluid. Thick fluids move more slowly and cause greater resistance to flow than thin fluids. The viscosity of blood depends on its red cell content. The greater the percentage of red cells in the blood, the more viscous the blood. This relationship is expressed as the hematocrit—the ratio of the volume of red blood cells to the volume of whole blood (see Chapter 25). A high hematocrit reduces flow through the blood vessels, particularly the microcirculation (arterioles, capillaries, venules). Conditions in which the hematocrit is elevated, such as dehydration, cyanotic congenital heart disease (see Chapter 31), or polycythemia (see Chapter 26), can lead to increased cardiac work as a result of increased vascular resistance.

The viscosity of blood also increases if blood flow becomes very slow or stagnates (anomalous viscosity). Anomalous viscosity is generally not significant unless cardiac output is low. (Shock is described in Chapter 46.)

Poiseuille’s formula for resistance to fluid flow through a tube takes into account the length of the tube, the viscosity of the fluid, and the radius of the tube’s lumen. Resistance (R) is proportional to a constant 8/π, the viscosity of the blood (η), and the length of the vessel (l), and it is inversely proportional to the fourth power of the lumen’s radius (ν⁴).² Thus

Because this equation was derived using straight, rigid tubes with steady streamlined flow, it cannot be applied directly to the vascular system. Nevertheless, it is a useful model of vascular resistance.

The most important factor determining resistance in a single vessel is the caliber of the vessel’s lumen, expressed in Poiseuille’s formula as its radius and in Figure 29-32 as its diameter. Small changes in the lumen’s radius lead to large changes in vascular resistance. Because vessel length is relatively constant, length is not as important as lumen size in determining flow through a single vessel.

Generally, resistance to flow is greater in longer tubes because resistance increases with length. That resistance increases with increased length is demonstrated by comparing flow of the same amount of blood under the same pressure through vessels arranged in different configurations. Blood flowing through the distributing arteries, beginning with branches off the aorta and ending at arterioles in the capillary bed, encounters more resistance than blood flowing through the capillary bed itself, where flow is distributed among many short, tiny branches arranged in parallel. This is because the distributing arteries comprise a long system of tubes connected in series (end-to-end), whereas the arterioles and capillaries comprise a short system of many vessels arranged in parallel (side by side) (Figure 29-33). Although the arterioles are arranged in series with the distributing arteries and the capillaries, they are arranged in parallel with other arterioles. Similarly, the capillaries are in series with the metarterioles, but they are in parallel with other capillaries.

Resistance to flow through a system of vessels, or total resistance, depends not only on characteristics of individual vessels but also on whether the vessels are arranged in series or in parallel (see Figure 29-30). For vessels arranged in series, total resistance equals the sum obtained by adding all the individual resistances calculated using Poiseuille’s formula. For vessels arranged in parallel, total resistance equals the sum of the reciprocals (I/R) of the individual resistances.

Total resistance is related to the total cross-sectional area of a system of vessels in parallel and to the number of vessels in parallel that make up the total cross-sectional area. The larger the total cross-sectional area, as in the capillary system, the lower the resistance. However, if a cross-sectional area is made up of a very large number of parallel vessels, the overall resistance will be greater than it would be if the cross-sectional area were made up of only two or three parallel vessels. Therefore, resistance is greater in smaller vessels than in larger vessels. The total cross-sectional area of the arteriolar system is greater than that of the arterial system (see Figure 29-32); the greater number of arterioles arranged in parallel, however, leads to greater resistance to flow in the arteriolar system. The pressure drop is greatest across the arterioles. Many capillaries arise from each arteriole so that the total cross-sectional area of the capillary bed is very large and resistance is low, despite the fact that the cross-sectional area of each capillary is less (which normally increases resistance) than that of each arteriole. As a result, blood flow becomes quite slow in the capillaries, analogous to water flow in a river. A narrow river whose bed widens flows more slowly through the wide section than through the narrow section. The slow velocity of flow in each vessel promotes optimal capillary-tissue exchange.

Velocity

Blood velocity is the distance blood travels in a unit of time, usually centimeters per second (cm/sec). Blood velocity is directly related to blood flow (amount of blood moved per unit of time) and inversely related to the cross-sectional area of the vessel in which the blood is flowing.

The relationship between velocity and flow can be understood by thinking of a river. The volume of water flowing in a river is the same whether the river is narrow or wide. Where the river narrows, the water flows quickly; where it widens, the water flows slowly. The volume of water moving between the riverbanks does not change. In the body, as blood moves from the aorta to the capillaries, the total cross-sectional area of the vessels increases and velocity of flow decreases.

Laminar Versus Turbulent Flow

Flow through any tubular system is either laminar or turbulent. Normally, blood flow through the vessels is laminar. In laminar flow, concentric layers of molecules move “straight ahead.” Each concentric layer flows at a different velocity (Figure 29-34). The cohesive attraction between the fluid and the vessel wall prevents the molecules of blood that are in contact with the wall from moving. The next thin layer of blood is able to slide slowly past the stationary layer and so on until, at the center, the blood velocity is greatest. The centermost concentric layer of fluid is not slowed by friction against the vessel wall. Large vessels have room for a large center layer; therefore, they have less resistance to flow and greater flow and velocity than smaller vessels.

Where flow is obstructed, the vessel turns, or blood flows over rough surfaces, it becomes turbulent with whorls or eddy currents that produce noise, causing a murmur to be heard on auscultation. Resistance increases with turbulence.

Vascular Compliance

Vascular compliance is the increase in volume a vessel is able to accommodate for a given increase in pressure (e.g., C = VP). Compliance depends on the ratio of elastic fibers to muscle fibers in the vessel wall. The elastic arteries are more compliant than the muscular arteries; the veins are more compliant than either type of artery and serve as storage areas for the circulatory system.

Compliance determines a vessel’s response to pressure changes. For example, with a very small increase in pressure, a large volume of blood can be accommodated by the venous system. In the less compliant arterial system, where smaller volumes and higher pressures are normal, small variations in pressure cause little or no change in the volume of blood within the arterial vessels.

Stiffness is the opposite of compliance. Several conditions and disorders can cause stiffness, with the most common being arteriosclerosis (see Chapter 30). Arteriosclerosis increases the rigidity or stiffness of arterial walls, which in turn increases peak arterial pressure at a given volume of blood.

Effects of Cardiac Output

The cardiac output (minute volume) of the heart can be changed by alterations in heart rate, stroke volume (volume of blood ejected during each ventricular contraction), or both. An increase in cardiac output without a decrease in peripheral resistance will cause arterial volume and mean blood pressure to increase. The higher arterial pressure increases blood flow through the arterioles. On the other hand, a decrease in the cardiac output causes an immediate drop in mean arterial blood pressure and arteriolar flow (Table 29-3).

Effects of Total Peripheral Resistance and Blood Volume

Total resistance in the systemic circulation, sometimes called total peripheral resistance, is determined primarily by change in the diameter of the arterioles. Arteriolar constriction raises mean arterial pressure by preventing the free flow of blood into the capillaries. Dilation has the opposite effect.

Venous Pressure

The main determinants of venous blood pressure are (1) the volume of fluid within the veins and (2) the compliance (distensibility) of the vessel walls. Veins have much thinner walls than arteries and are more distensible than arteries. The venous system accommodates approximately 60% of the total blood volume at any given moment, with venous pressure averaging less than 10 mmHg. Conversely, the arteries accommodate about 15% of the total blood volume, with an average arterial pressure (blood pressure) of about 100 mmHg.

The sympathetic nervous system controls compliance. The walls of the veins are highly innervated by sympathetic fibers that when stimulated cause venous smooth muscle to contract. This increases smooth muscle tone rather than causing vasoconstriction, as occurs in arterial vessels. The effect of increased smooth muscle tone is to stiffen the wall of the vein, which reduces distensibility and increases venous blood pressure, forcing more blood through the veins and into the right heart.

Two other mechanisms that increase venous pressure and venous return to the heart are (1) the skeletal muscle pump and (2) the respiratory pump. During skeletal muscle contraction the veins within the muscles are partially compressed, causing a decrease in venous capacity and increased return to the heart. The respiratory pump acts during inspiration, when the veins of the abdomen are partially compressed by the downward movement of the diaphragm. Increased abdominal pressure moves blood toward the heart.

Autoregulation

Autoregulation (automatic self-regulation) enables individual vessels to regulate blood flow by altering their own arteriolar resistances. Autoregulation in the coronary circulation maintains constant blood flow at perfusion pressures (mean arterial pressure) between 60 and 180 mmHg when other influencing factors are held constant. Thus autoregulation ensures constant coronary blood flow despite shifts in the perfusion pressure within the stated range.

The mechanism of autoregulation is not known, but two explanations have been proposed: the myogenic hypothesis and the metabolic hypothesis. The myogenic hypothesis proposes that autoregulation originates in vascular smooth muscle, presumably of the arterioles, as a response to changes in arterial perfusion pressure. Increased coronary perfusion pressure increases the pressure against the vessel wall and the stretch increases the vessel’s radius, resulting in an increase in wall tension. Initially, coronary blood flow increases with the abrupt distention of the blood vessels. The stretching eventually stimulates contraction of the smooth muscles, which increases vascular resistance. The return of more normal flow follows constriction of the arterioles. Because stretch of vascular smooth muscle increases intracellular Ca⁺⁺, it is proposed that an increase in transmural pressure activates membrane calcium channels.¹ This mechanism also works in the opposite direction; that is, vasodilation is stimulated by decreased arterial pressure.

The metabolic hypothesis of autoregulation, which is better documented, proposes that autoregulation of coronary vessels originates in the myocardium. The stimulus is a drop in coronary perfusion pressure or an increase in the metabolic needs of the myocardium (e.g., because of strenuous exercise). With an increased myocardial oxygen requirement, myocardial cells release substances that promote vasodilation. Substances implicated include CO₂, hydrogen ions (lactic acid), potassium ions, and adenosine. The best known of these substances is adenosine, a potent vasodilator released in response to a decrease in myocardial oxygenation.¹ An increased concentration of adenosine in the interstitial fluid decreases the resistance of the coronary arterioles and increases blood flow. Perfusion strongly correlates with the amount of adenosine released. When coronary perfusion pressure is increased, the increased flow washes out the vasodilatory substances. As the dilators are washed out, vasoconstriction occurs and returns flow toward normal.

Autonomic Regulation

As described, stimulation of the sympathetic nerves to the heart causes a marked increase in coronary blood flow, even though it also causes vasoconstriction of the coronary vessels. The increased coronary flow is caused by the increase in myocardial metabolism created by the sympathetic stimulation of the heart rate and contractility. The release of vasodilatory metabolites, such as adenosine, from the increased myocardial activity tends to overwhelm the coronary vasoconstriction. Thus metabolic autoregulation overrides neurogenic influences, and the net effect of sympathetic stimulation is to increase coronary blood flow.¹

Cardiography

Electrocardiography, typically the 12-lead electrocardiogram (ECG), gives information about heart rate and rhythm, the effects of electrolytes or drugs on the heart, and the electrical orientation of the cardiac muscle. An ECG gives no direct information about the contractile state or mechanical performance of the heart.

Serial 12-lead ECGs are of primary importance in establishing the presence of myocardial ischemia and infarction or conduction defects and dysrhythmias. This examination has become part of the routine hospital admission assessment, even when the admitting diagnosis is not cardiac in nature, because it establishes baseline information about the electrical function of the heart. Also recent ECGs can be compared with ECGs obtained from the same individual in the past. Changes in the ECG over time assist in determining the cause, amount, or nature of changes in cardiac anatomy and physiology.

Chest Radiograph Examination

Chest x-rays allow for the examination of the size and contour of the heart and related structures. Evidence of chamber enlargement, pericardial disease, pulmonary edema, valvular calcification, and pathology of the great vessels may be visualized. Chest x-ray is also useful to look for appropriate placement of invasive cardiac devices and for any complications thereof (e.g., pneumothorax or hemothorax; see Chapter 33). A chest x-ray examination is a routine part of a cardiac examination. The most commonly obtained views are posteroanterior (PA) and lateral, with the individual standing upright and the lungs fully expanded. In those individuals confined to bed, an anteroposterior (AP) view may be obtained but is usually of lesser quality than the PA.

Stress Testing

Cardiac activity during exercise is examined during a stress test. Stress testing elicits signs and symptoms of heart disease and coronary artery disease that may not appear at rest. Continuous 12-lead ECG and blood pressure measurement are obtained before, during, and after the study. Cardiac stress from exercise is induced by having the individual walk on a treadmill. Other, less frequently used forms of exercise include static exercise (hand ergometry or chemical stress), stair climbing (the Stairmaster’s double two-step), arm ergometry, and bicycle ergometry. The individual exercises until the maximal heart rate for gender and age is reached or until other subjective or objective indicators of cardiac dysfunction or distress appear. Subjective indicators include chest pain, extreme fatigue, extreme dyspnea, leg pain, or the individual’s request to stop the test. Objective criteria are ST segment elevation or depression, SA node or atrial dysrhythmias, AV node dysrhythmias, ventricular dysrhythmias, elevated or decreased blood pressure, signs of cerebral hypoxia, and signs of circulatory insufficiency.

A stress test is useful also in determining the rate or progress of recovery from a myocardial infarction or cardiac surgery. Graded exercise in individuals with low- to moderate-risk chest pain evaluated in an emergency department can be used as a prognostic indicator of adverse cardiac events. When a differential diagnosis for chest pain has been difficult to determine, stress testing may help distinguish coronary artery insufficiency from other causes of pain. There is some risk associated with stress testing. The risk is greater when the test is performed soon after an acute ischemic event.

Stress testing with ECG monitoring may not be sensitive enough to detect and localize areas of the myocardium at risk for ischemia and infarction. Currently, most stress testing includes the injection of a radiotracer that is taken up by active heart cells. When the heart is scanned, during and after stress testing, areas where the radiotracer is not taken up by ischemic cells can be seen and therefore localizes areas of myocardial damage and risk.

Single-Photon Emission Computed Tomography

Single-photon emission computed tomography (SPECT) is the most commonly used tool for evaluating individuals for coronary artery disease and myocardial ischemia during stress testing. A radiotracer (usually thalium-201) is injected intravenously and is taken up by healthy myocytes and retained for some period of time.³⁸ Photons are emitted from the myocardium in proportion to perfusion of the tissue. A gamma camera visualizes the photons, and views are taken from 360 degrees by CT, which digitizes the information and provides a three-dimensional view. Data about where the myocardium take up the tracer normally, slowly, or not at all can be correlated with existing myocardial disease and can help quantify ischemic risk.

Echocardiography

Echocardiography is the most effective noninvasive modality for evaluating the structures of the heart. Ultrasound beams reflected by cardiovascular structures produce shapes that can be visualized and allow for recognition of altered cardiac anatomy.³⁸ It is used to evaluate for suspected heart failure, valvular disease, infective endocarditis, cardiomyopathies, pericardial disease, and congenital heart disease. Through the use of two-dimensional techniques with Doppler and color flow imaging, accurate assessments of cardiac output, ejection fraction, and valvular function can be obtained.

Computed Tomography and Magnetic Resonance Imaging

Initially, CT and MRI had limited roles in the evaluation of heart disease because they required structures to be still in order to provide clear images. New techniques, including ECG gating (timing of gathering the data to the cardiac cycle), have greatly expanded the use of these two modalities³⁸ that can evaluate cardiac anatomy and physiology. Improvements such as electron beam CT and spiral CT have improved the ability of tomography to visualize cardiac structures. The high resolution of CT can provide information about calcification of coronary vessels and cardiac valves. It is also an essential tool for evaluating large-vessel disease.

MRI is based on the principle that the frequency of energy (resonant frequency) given up by a nucleus is exactly proportional to the surrounding magnetic field³⁸ (see Chapter 14). Anatomy and physiology of the great blood vessels and myocardium are depicted in three dimensions with excellent resolution. Ventricular function can be evaluated using indices of ventricular function, such as ejection fraction. Rapidly moving sequences (MRI) can determine regional wall motion and myocardial deformation. Flow direction and velocity also can be quantitatively determined.

Technetium Scanning

Technetium pyrophosphate (^99mTcPYP) is injected intravenously into a resting individual during a “hot spot” imaging examination. Two hours after injection the distribution pattern of the radioactive solution is recorded by nuclear scan. During the 2-hour delay, the injected material will have been taken up by infarcted areas of the myocardium, particularly 1 to 3 days after the onset of symptoms. This study is not definitive during the first 12 hours after an infarct.

Technetium scanning is used when (1) there is a conflicting history for myocardial infarction, (2) there are equivocal ECG abnormalities, or (3) an individual’s cardiac enzymes have been elevated because of surgery or trauma. Such small amounts of the injected material are used in this examination that the risks associated with radioactive substances are not an issue.

Electrophysiology Studies

In-depth evaluation of electrical conduction within the heart can provide important information about the nature and causes of dysrhythmias, such as atrial and ventricular tachycardias and heart block. There are many types of electrophysiology studies that are specific to certain conduction disorders but they have the common goal of documenting abnormal conduction pathways. Furthermore, the techniques used may also allow for ablation of unwanted pathways or the appropriate placement of stimulating devices (pacers).

One example of an electrophysiology study is AV bundle electrocardiography. Two electrode-tipped catheters are inserted percutaneously into the femoral vein, floated up the inferior vena cava, and positioned in or near the right atrium during AV bundle (His bundle) electrocardiography. AV bundle electrocardiography can detect secondary sites of impulse generation (ectopic foci), as well as accessory pathways of conduction. Other conduction defects and the effects of drugs on conduction also can be illuminated. Risks related to this procedure can be grave and include dysrhythmias, death, vessel or heart perforation, clot or plaque embolization, and kidney failure.

Cardiac Catheterization and Angiography

One or both sides of the heart can be examined using cardiac catheterization. This procedure requires the use of fluoroscopy and strict sterile techniques and takes place in a specially equipped catheterization laboratory. Local anesthesia is given, and a catheter is introduced percutaneously into the vasculature and passed caudally into the atrium and ventricle. For a right-heart catheterization, the catheter is placed in the jugular, subclavian, brachial, or femoral vein. The femoral artery is commonly used for a left-heart study. Once the catheter has been guided into the atrium, pressures are recorded, blood samples are obtained to examine oxygen content, and a contrast medium is injected to visualize chamber function and valve patency. The catheter is then passed into the ventricles and the sequence is repeated.

Cardiac catheterization provides a means to visualize the chambers of the heart continuously, although for a short time. A great deal of information can be obtained about heart structure and function. Pressures in each chamber and across heart valves can be precisely measured, along with timing of events in the cardiac cycle. Of particular value is the ability to compare the oxygen content of blood in each heart chamber. Risks for this procedure have decreased over time. One of the most serious complications of cardiac catheterization is the development of dysrhythmias. Death usually is caused by cardiac arrest after ventricular fibrillation.

Fluoroscopic visualization of the coronary arteries and left-heart structures using contrast dye is called coronary angiography or arteriography. Like cardiac catheterization, this study takes place in a catheterization laboratory using local anesthesia and a sterile field. A catheter is threaded into the left ventricle through the femoral artery. A ventriculogram generally is performed first. Contrast dye is injected into the apex of the ventricle, and the next few cardiac cycles are visualized and filmed. Like cardiac catheterization, coronary angiography is used to gain information about the structure and function of the ventricles and related valves. After the ventriculogram, catheters are introduced individually into the ostia of the coronary arteries. When the catheter is in position, 5 to 10 ml of contrast dye is mechanically and rapidly injected into the artery and the results are visualized and filmed. Dye injection is repeated with the individual tilted at various angles to afford views of the artery other than the anteroposterior view. The catheter is then either moved to the next artery to be studied or withdrawn to conclude the study.

The risks of this procedure are similar to those of cardiac catheterization, with exceptions. Because the blood supply to the cardiac muscle is briefly interrupted when dye is introduced into the coronary arteries, angina (chest pain) caused by ischemia (lack of oxygen) is much more common. Coronary artery spasms also can occur. Interrupted flow also causes decreased heart rate (bradycardia), as well as some tachydysrhythmias, hypotension, and ST segment depression.

Pulse Tracing

Pulsation, described by the flow of blood through an artery during the cardiac cycle, can be drawn as a waveform plotting pressure against time (Figure 29-43). The waveform can be obtained noninvasively by placing a transducer on the skin over the carotid artery while the individual’s head is turned slightly away from the transducer. The amplitude and shape of arterial waveforms can provide information about arterial stiffening and adequacy of perfusion.

Doppler Ultrasonography Studies

A Doppler study is made by using a handheld microphone placed on the skin over a lubricating gel. The microphone amplifies and can record sounds made by blood flowing in peripheral vessels. The Doppler microphone is placed over the vessel to be studied, and sounds related to obstructions to flow, vessel wall mobility, and heart murmurs are transmitted through the gel to the microphone. The microphone amplifies sound waves so that they are audible to the human ear. Ultrasound techniques can be used to digitize the audio findings into visual findings that can be analyzed for flow velocity and volume. These studies are useful in the evaluation for abnormalities of venous flow (e.g., deep venous thrombosis) and arterial flow (e.g., embolism).

Computed Tomography and Magnetic Resonance Imaging

CT and MRI, used to evaluate the systemic circulation, provide information about the structure of the great vessels. Either can be used to evaluate for aneurysms and dissections of the thoracic or abdominal aorta. CT also can be used to assess for vessel calcification and provide some insights into the risk for stroke and myocardial infarction through evaluation of the carotid and coronary vessels.

Venography and Arteriography

Radiopaque dye can be injected through intravenous or intra-arterial catheters to allow for visualization of the internal structure, diameter, and patency of veins and arteries. Venography is performed primarily in the lower extremity to assess for the presence of thrombi in the large veins of the leg. Arteriography (angiography) can be used in almost any vascular system, including the great vessels, pulmonary, coronary (see previously in this chapter), cerebral, mesenteric, renal, hepatic, and peripheral arteries. Risks include rupture, dissection, thrombosis, embolization, or organ infarction involving the arterial system being studied.

KEY TERMS

a wave 1096

Adrenomedullin (ADM) 1128

Afferent lymphatic vessel 1133

Afterload 1109

Aldosterone 1127

Angiogenesis 1097

Angiotensin I (Ang I) 1125

Angiotensin II (Ang II) 1125

Anisotropic band (A band) 1106

Anomalous viscosity 1119

Anterior interatrial myocardial band (Bachmann bundle) 1102

Antidiuretic hormone (ADH) 1125

Aorta 1095

Aortic semilunar valve 1094

Arteriogenesis 1097

Arteriole 1113

Arteries 1113

AT₁ 1127

AT₂ 1127

Atrial natriuretic peptide (ANP or factor) 1128

Atrioventricular (AV) node 1101

Atrioventricular valve 1094

Automatic cell 1103

Automaticity 1103

Bainbridge reflex 1112

Baroreceptor reflex 1112

Brain natriuretic peptide (BNP) 1128

Bundle branch 1101

Bundle of His (atrioventricular bundle, common bundle) 1101

c-type natriuretic peptide (CNP) 1128

c wave 1096

Calcium channel–blocking drug 1108

Capillary 1113

Cardiac action potential 1099

Cardiac catheterization 1135

Cardiac cycle 1095

Cardiac output 1109

Cardiac plexus 1104

Cardioexcitatory center 1112

Cardioinhibitory center 1112

Cardiovascular control center 1111

Chordae tendineae 1094

Circumflex artery 1097

Collateral artery 1097

Conduction system 1099

Coronary angiography 1135

Coronary perfusion pressure 1130

Coronary sulcus 1097

Crista supraventricularis 1095

Cross-bridge theory of muscle contraction 1108

Depolarization 1102

Diastole 1095

Diastolic depolarization 1103

Efferent lymphatic vessel 1133

Ejection fraction 1109

Elastic artery 1113

End-diastolic volume 1110

Endocardium 1093

Endothelial cells 1116

Endothelium 1116

Epinephrine 1125

Excitation-contraction coupling 1108

Fenestration 1113

Frank-Starling law of the heart 1109

Great cardiac vein 1099

Heart rate 1099

Hyperemia 1125

Inferior vena cava 1095

Inflow tract 1094

Inotropic agent 1111

Insulin 1130

Intercalated disk 1105

Isotropic band (I band) 1106

Laminar flow 1121

Left anterior descending artery (LAD) 1097

Left atrium 1093

Left bundle branch (LBB) 1102

Left coronary artery (LCA) 1096

Left heart 1091

Left pulmonary artery 1095

Left ventricle 1093

Left ventricular end-diastolic pressure (LVEDP) 1110

Left ventricular end-diastolic volume (LVEDV) 1110

Lumen 1113

Lymph 1132

Lymphatic system 1131

Lymphatic vein 1132

Lymphatic venule 1132

M line 1106

Mean arterial pressure (MAP) 1122

Mediastinum 1093

Metarterioles 1113

Middle internodal pathway 1102

Mitral and tricuspid complex 1094

Mitral valve 1094

Muscular artery 1113

Myocardial contractility 1108

Myocardial oxygen consumption () 1107

Myocardium 1093

Myoglobin 1131

Myosin 1106

Node 1099

Norepinephrine 1125

Outflow tract 1094

P cell 1100

P wave 1103

Papillary muscle 1094

Parietal pericardium 1093

Perfusion 1122

Pericardial cavity 1093

Pericardial fluid 1093

Pericardium 1093

Peripheral vascular system 1113

Poiseuille’s formula 1119

Posterior internodal pathway 1102

Posterior vein of the left ventricle 1099

Precapillary sphincter 1113

Preload 1109

Pressure 1117

PR interval 1103

Pulmonary artery 1095

Pulmonary circulation 1091

Pulmonary veins 1095

Pulmonic semilunar valve 1094

Purkinje fiber 1102

QRS complex 1103

QT interval 1103

Renin 1125

Renin-angiotensin aldosterone system (RAAS) 1126

Repolarization 1102

Resistance 1118

Rhythmicity 1103

Right atrium 1093

Right bundle branch (RBB) 1101

Right coronary artery (RCA) 1096

Right heart 1091

Right lymphatic duct 1132

Right pulmonary artery 1095

Right ventricle 1093

Semilunar valve 1094

Shear stress 1097

Sinoatrial node (SA node, sinus node) 1100

ST interval 1103

Stroke volume 1109

Superior vena cava 1095

Systemic circulation 1091

Systole 1095

Systolic compressive effect 1131

Thoracic duct 1132

Tissue-based renin-angiotensin system 1127

Total resistance 1120

Trabeculae carneae 1096

Tricuspid valve 1094

Troponin 1106

Troponin C 1106

Troponin T 1106

Troponin-tropomyosin complex 1106

Tunica externa (adventitia) 1113

Tunica intima 1113

Tunica media 1113

Turbulent 1121

Urodilatin 1128

v wave 1096

Vasa vasorum 1113

Vascular compliance 1122

Vasoconstriction 1113

Vasodilation 1113

Vasomotion 1116

Vein 1113

Venule 1113

Visceral pericardium (epicardium) 1093

x descent 1096

y descent 1096

Z line 1106