How does an understanding of the mechanisms of the heart help you in treatment of your patient regardless of the illness? How does basic cardiac monitoring factor into caring for your patient? How do you care for patients with dysrhythmia? Share some of your best practices. #1 source must be from textbook, chapters 17 & 18 attached (see bellow reference ) Sources (2) 1. Jacquelyn L. Banasik Ph.D. Arnp. (2018). Pathophysiology (6th ed.). Saunders
17
Cardiac Function
Jacquelyn L. Banasik
CHAPTER OUTLINE
KEY QUESTIONS
The primary function of the heart is to produce the driving force that propels blood through the vessels of the circulatory system. Along with the lungs, the heart works to distribute oxygenated blood and nutrients to tissues and organs of the body. Complex regulatory mechanisms function to match the cardiac output with the metabolic needs of the tissues. Cardiac dysfunction can lead to abnormal function or death of cells in tissues throughout the body. Cardiovascular disease is the leading cause of mortality in the United States, and a significant proportion of the population suffers from physical limitations associated with impaired cardiac function. Familiarity with cardiac anatomy and physiology is requisite to understanding cardiac diseases and therapy.
Cardiovascular Anatomy
Heart
The heart is located in the mediastinum, suspended between the lungs; behind the sternum; and in front of the vertebral column, thoracic aorta, and esophagus (Fig. 17.1). When viewed from the front, the heart appears to be rotated to the left so that the right atrium and right ventricle are most anterior. The base of the heart protrudes somewhat into the right side of the chest and is relatively fixed in place by its attachments to the great vessels. The apex of the heart lies primarily in the left side of the chest and is directed forward toward the anterior chest wall. With each heartbeat, a characteristic thrust, or point of maximal impulse (PMI), is generated and can be palpated where the apex strikes against the chest. The PMI is normally located on the left side of the chest where the fifth intercostal space and midclavicular line intersect. Variations in heart size and position within the chest may be related to age, body size, shape, weight, or pathologic conditions of the heart and other nearby structures.
FIG 17.1 Position of the heart in the mediastinum. The base of the heart protrudes into the right side of the chest, whereas the apex lies in the lower left side of the chest.
Functionally important cardiac tissues include connective tissues, which form the fibrous skeleton and valves; cardiac muscle, which produces the contractile force; and epithelial tissue, which lines the cardiac chambers and covers the outer surfaces of the heart. The fibrous skeleton includes an extensive network of matrix that supports cardiac cells and four rings that provide a firm scaffold for attachment of the cardiac valves (Fig. 17.2). Four cardiac valves control the direction of blood flow through the heart (Fig. 17.3). The mitral valve (bicuspid) directs blood flow from the left atrium to the left ventricle, whereas the tricuspid valve directs blood from the right atrium to the right ventricle. The edges of these atrioventricular (AV) valves are attached to rings formed by the fibrous skeleton. Valve leaflets are tethered to papillary muscles of the ventricular chambers by connective tissues called chordae tendineae. Papillary muscles attach to ventricular walls and help prevent the valve leaflets from bending backward into the atria during ventricular contraction (Fig. 17.4). The AV valves open passively during diastole when the pressure of blood in the atria exceeds that in the ventricles. Ventricular contraction reverses the pressure gradient and causes AV valves to snap shut, preventing blood from flowing backward into the atria.
FIG 17.2 Connective tissue extracellular matrix of the heart with all cells removed developed by Dr. Doris Taylor’s lab. (Image provided by Regenerative Medicine Research Labs at Texas Heart Institute.)
FIG 17.3 A, Position of the heart valves as viewed from above. B, Configuration of the heart valves showing the two cusps of the mitral valve and the three cusps of the tricuspid valve. The pulmonary and aortic valves have three leaflets.
FIG 17.4 Chordae tendineae and papillary muscles attach the mitral and tricuspid valve leaflets to the ventricular myocardium.
Two semilunar valves are located in the ventricular outflow tracts. The pulmonic valve lies between the right ventricle and pulmonary artery, and the aortic valve lies between the left ventricle and aorta. Compared with the AV valves, the semilunar valves are thicker and are not supported by fibrous cords. They open and close passively according to pressure gradients, just as the AV valves do. When intraventricular pressures exceed pulmonary and aortic pressures, the semilunar valves remain open and then close when ventricular pressures fall below aortic and pulmonary artery pressures.
The cardiac muscle layer (myocardium) produces the contractile force that pushes blood through the circulatory system. Heart muscle is organized into four separate chambers of varying muscular wall thickness, reflecting the degree of pressure each chamber must generate to pump blood. Atria serve primarily as conduits and have a thinner layer of muscle than the ventricles. The left ventricular muscle is two to three times thicker than that of the right ventricle because higher pressures are required to eject blood into the systemic circulation than into the pulmonic system. Normal chamber pressures are shown in Table 17.1. Alterations in chamber pressures may reflect pathologic cardiovascular changes such as valvular disorders, blood volume abnormalities, and heart failure (see Chapters 18 and 19).
TABLE 17.1
| Normal Pressures in the Heart | |
| Location | Pressure (mm Hg)* |
| Right atrium | 0–8 |
| Right ventricle | 15–28/0–8 |
| Pulmonary artery | 15–28/4–12 |
| Left atrium | 4–12 |
| Left ventricle | 100–120/4–12 |
| Aorta | 100–120/60–80 |
*Right and left atrial pressures listed as means; other pressures written as systolic/diastolic.
Cardiac chambers and valves are lined by a layer of squamous epithelial cells called the endocardium. The endocardial layer provides a smooth surface that prevents clotting and minimizes trauma to red blood cells. The endocardium is continuous with the endothelium of the vascular system. Outer surfaces of the heart are also covered by a layer of epithelial cells called the epicardium, which is part of a protective covering called the pericardium. The pericardium is composed of two layers that envelop the heart like a sac (Fig. 17.5). The inner layer (visceral pericardium or epicardium) is attached directly to the heart’s outer surface, whereas an outer layer (parietal pericardium) forms a sac around the heart. The parietal pericardium is composed of an epithelial layer and a tough fibrous layer.
FIG 17.5 Pericardial sac is composed of two layers separated by a narrow, fluid-filled space. The visceral pericardium (epicardium) is attached directly to the heart’s surface, whereas the parietal pericardium forms the outer layer of the sac.
Visceral and parietal pericardial layers are separated by a thin, fluid-filled space (pericardial space) that usually contains 10 to 30 mL of serous fluid. This fluid lubricates pericardial surfaces and reduces friction while the layers slide against one another during cardiac contraction. Accumulations of fluid in the pericardial space or inflammation of the pericardial sac can restrict cardiac filling and impair cardiac output.
Circulatory System
The circulatory systems of the lungs and body can be viewed as two separate but interdependent systems (Fig. 17.6). The left-sided heart chambers produce the force to propel blood through the vessels of the systemic (body) circulation. The left atrium receives oxygenated blood from the lungs by way of the pulmonary veins and delivers it to the left ventricle. This oxygenated blood is pumped by the left ventricle into the aorta, which supplies the arteries of the systemic circulation. Venous blood is collected from capillary networks of the body and returned to the right atrium by way of the vena cavae. Blood from the head returns to the right atrium through the superior vena cava; blood from the body returns via the inferior vena cava. There are no valves between the vena cavae and the right atrium, and the atrial pressure waves that are generated during the cardiac cycle cause characteristic visible pulsations in the jugular veins. An increased right atrial pressure may be observed as distention within the jugular veins.
FIG 17.6 Systemic and pulmonary circulations viewed as separate but interdependent systems. The right ventricle pumps blood through the pulmonary vasculature, whereas the left ventricle pumps blood through the systemic circulation.
The right side of the heart receives deoxygenated blood from the systemic circulation and pumps it through the lungs by way of the pulmonary artery. The pulmonary artery divides into left and right branches, which subdivide to supply blood to pulmonary capillary beds. Exchange of respiratory gases occurs at the pulmonary capillaries so that blood delivered to the left atrium by the pulmonary veins is well oxygenated.
Blood flow through the left and right heart chambers is connected in series such that the output of one becomes the input of the other. Thus the functions of the right and left sides of the heart are interdependent. Failure of one side of the heart to pump efficiently soon leads to dysfunction of the other side.
Characteristic changes in the anatomy and physiologic functioning of the heart and circulatory systems occur with aging (see Geriatric Considerations: Changes in the Heart). In general, these changes result in a decreased cardiac reserve and a greater predisposition to cardiac muscle ischemia.
Key Points
Cardiac Cycle
Each heartbeat is composed of a period of ventricular contraction (systole) followed by a period of relaxation (diastole). The interval from one heartbeat to the next is called a cardiac cycle and includes ventricular, atrial, and aortic (or pulmonic) events. Each of these events is associated with characteristic pressure changes within the cardiac chambers. Pressure changes result in valvular opening and closing and unidirectional movement of blood through the heart. The various events of the cardiac cycle are illustrated as a function of time in Fig. 17.7. Another method of graphing ventricular function is the pressure–volume loop (Fig. 17.8). Pressure–volume loops are useful for assessing the relationships between pressure and volume at various points in the cardiac cycle to evaluate left ventricular function. Abnormalities in these waveforms may occur with diseases of the cardiac valves, changes in blood volume, or changes in pumping capacity of the heart (see Chapter 18). These waveforms are commonly monitored with specialized cardiac catheters in patients with cardiac or hemodynamic disorders.
FIG 17.7 Events of the cardiac cycle showing relationships among left atrial and ventricular pressures, ventricular volume, and aortic pressure. An identical set of events occurs on the right side of the heart, although pressures are lower.
FIG 17.8 Pressure–volume loop showing changes in left ventricular volume and pressure during the cardiac cycle.
The cardiac cycle can be described sequentially, beginning with ventricular filling. During diastole the ventricles are relaxed and blood flows in from the atria through open AV valves. Initially, ventricular filling occurs passively because of a pressure gradient between the atria and ventricles. Toward the end of ventricular diastole, the atria contract, squeezing more blood through the AV valves into the ventricles. The “atrial kick” provided by atrial contraction is particularly important during fast heart rates, when the time for ventricular filling is shortened; the atrial contraction helps load the ventricle quickly to prevent a reduction in stroke volume. Ventricular events include isovolumic contraction, ejection, and isovolumic relaxation. Each of these cycle events is further described in the following sections.
Isovolumic Contraction
Immediately after atrial systole the ventricles begin to contract, causing intraventricular pressure to rise and the AV valves to close. AV valve closure produces a sound that can be heard at the chest wall and is termed S1. Ventricular pressure rises rapidly during isovolumic contraction because all four cardiac valves are closed, and the volume of blood within the ventricular chamber is forcefully compressed by the powerful ventricular myocardium (see Fig. 17.7, red tracing). Volume remains constant during this phase. The rate of rise in pressure is an indication of the contractile state of the heart. The greater the change in pressure per unit time (dP/dt), the higher the contractile state. Sympathetic nervous system activation increases dP/dt, whereas conditions such as heart failure are characterized by a slower rate of pressure development. The term inotropy is commonly used interchangeably with contractility and is reflected by the velocity and degree of cardiac muscle shortening during systole.
Ventricular Ejection
Ventricular contraction results in a rapid rise in ventricular pressure. As ventricular pressure exceeds aortic pressure (or pulmonic), the valve is forced open and a period of rapid ejection of blood from the ventricle follows. The rapid ejection phase is followed by a period of reduced ejection as aortic (or pulmonic) pressure rises and ventricular pressures and volumes fall. The amount of blood ejected with each contraction of the ventricle is called the stroke volume (SV), the volume of blood in the ventricle before ejection is the end-diastolic volume (EDV), and the amount of blood that remains in the ventricle after ejection is the end-systolic volume (ESV). Thus stroke volume equals EDV minus ESV. An important and commonly used index of pumping effectiveness is the ejection fraction (EF), which is calculated by dividing SV by EDV. A normal EF is 60% to 80%; patients with systolic heart failure often have an EF of less than 40%.
Geriatric Considerations
Changes in the Heart
With aging, there is a decrease in the number of myocytes, but normally the heart size does not change appreciably. With the loss of overall cardiac muscle tissue, a corresponding expansion occurs in myocardial collagen and fat. The left ventricular muscle wall becomes thicker, with a resulting increase in oxygen demand. The endocardium becomes fibrotic and sclerosed. Cross-linking of the collagen tissue within the heart muscle increases myocardial stiffening, which causes decreased compliance. The decrease in compliance produces a decline in cardiac contractility, which reduces the heart’s pumping ability. The rate of ventricular relaxation decreases.
Fibrotic changes in cardiac valves result from a combination of hemodynamic stress and generalized thickening. There is also a decrease in coronary artery blood flow to the myocardium, which affects myocardial oxygen and nutrient supply. The myocardial cells increase in size, with increased lipofuscin pigment and lipid deposition.
Within the specialized electrical conduction tissue, there is loss of myocytes and fibrosis of conduction pathways, especially in the sinoatrial (SA) node, AV node, and bundle of His. The number of pacemaker cells in the SA node decreases, resulting in less responsiveness of that node to adrenergic stimulation. Myocardial cell irritability increases. On the ECG, the P wave may be notched or slurred. The PR interval is longer, and the QRS amplitude decreases. The axis may shift left as a result of left ventricular muscle thickening (hypertrophy). The T wave may be notched, and the amplitude may decrease.
The changes previously noted affect cardiac function. The resting heart rate in the elderly is unchanged. During stress or exercise, the aging heart is unable to respond quickly with an elevated rate, and the maximal heart rate elevation is reduced. Once the heart rate is elevated, it takes a much longer time for the heart rate to return to the resting level. The cardiac stroke volume and cardiac output generally decrease with age. Oxygen consumption in the myocardium is reduced, resulting in less efficient function when stressed and an overall decreased cardiac reserve.
Isovolumic Relaxation
The isovolumic relaxation phase begins with semilunar valve closure in response to falling ventricular pressures and ends when the AV valves open to allow ventricular filling. Ventricular blood volume remains constant during this period because all four cardiac valves remain closed. Closure of the semilunar valves causes the second heart sound, S2. Opening of the AV valves signals the beginning of rapid ventricular filling and the start of another cardiac cycle. The rate of ventricular relaxation is indicated by the drop in ventricular pressure per unit time and is called the −dP/dt. The rate and degree of ventricular relaxation is called lusitropy and is an energy-requiring process that reflects the efficiency of calcium removal from the cytoplasm. Rapid relaxation is necessary to allow the ventricle to fill quickly and at a low pressure before the next systole. Impaired relaxation (lusitropic dysfunction) is a common finding in patients with heart failure and contributes to the symptoms of congestion (see Chapter 19). Because relaxation of the ventricle is an energy-requiring process, it may become impaired when blood flow and oxygen delivery to the heart are inadequate.
Atrial Events
Atrial pressure waves have three characteristic curves: a, c, and v (see Fig. 17.7, green tracing). The a wave corresponds to atrial contraction, which immediately precedes AV valve closure. The c wave occurs early in ventricular systole and is thought to represent bulging of AV valves into the atrial chambers. The v waves have a gradual incline, which represents filling of the atrium as blood returns from the circulation. The v wave drops rapidly as atrial pressure is relieved by AV valve opening. A large v wave is often associated with inadequate closure of the AV valve, resulting in regurgitation of ventricular blood back into the atrium during ventricular systole. The mean right atrial pressure, also called the central venous pressure, is commonly measured as an indicator of the blood volume in the heart, which is dependent in part on the amount of blood being returned from the systemic circulation.
Aortic and Pulmonary Artery Events
Aortic and pulmonary artery pressures rise and fall in relation to the cardiac cycle. Arterial pressures fall to their lowest value just before semilunar valve opening. This lowest pressure is called diastolic blood pressure. Arterial pressure reaches its maximum during ventricular ejection and is called systolic blood pressure. A characteristic notch (dicrotic notch) in the arterial pressure curve may be seen as the semilunar valves close (see Fig. 17.7, blue tracing).
The difference in aortic pressure between systole and diastole is partly dependent on the aorta’s elastic characteristics. During systole, the aorta stretches to accommodate blood ejected by the ventricle. The stretched aorta has “stored,” or potential, energy that is released during diastole to maintain driving pressure and to keep blood flowing continuously through the circulation. Aortic stiffening, as occurs with aging or arteriosclerosis, may result in higher systolic and lower diastolic blood pressures attributable to loss of aortic elastic properties. When aortic or pulmonic pressures are chronically elevated, the ventricles must generate more pressure to open the semilunar valves and eject the stroke volume. Over time this extra effort required to increase the pressure can damage the heart muscle and lead to hypertrophy or failure.
Key Points
Coronary Circulation
Anatomy of the Coronary Vessels
The blood supply to heart muscle is provided by the coronary arteries (Fig. 17.9). Right and left coronary artery openings are located in the sinuses of Valsalva, in the aortic root, just beyond the aortic valve. The right coronary artery originates near the aortic valve’s anterior cusp and passes diagonally toward the right ventricle in the AV groove. In approximately 50% of the population, the right coronary artery gives rise to a posterior descending vessel that supplies blood to the heart’s posterior aspect. In 20% of the population, the left coronary artery is dominant in supplying blood to the ventricles, and in 30% of the population the right and left coronary arteries deliver about the same amount of blood and neither is dominant. The left main coronary artery arises near the aortic posterior cusp and travels a short distance anteriorly before dividing into the left anterior descending and circumflex branches. The anterior descending branch supplies septal, anterior, and apical areas of the left ventricle, whereas the circumflex artery supplies the lateral and posterior left ventricle. The three major coronary arteries give rise to a number of smaller branches that penetrate the myocardium and branch into small arterioles and capillaries. Regular exercise and stable atherosclerotic plaques in the coronary arteries are thought to stimulate the development of more extensive collateral circulation in the heart. Collateral vessels may help limit infarct size in patients suffering acute coronary occlusions (see Chapter 18). Areas supplied by divisions of the coronary arteries are listed in Table 17.2. Most of the heart’s capillary beds drain into the coronary veins, which then empty into the right atrium through the coronary sinus (Fig. 17.10).
FIG 17.9 Coronary arteries supplying the heart. The right coronary artery supplies the right atrium, ventricle, and posterior aspect of the left ventricle in most individuals. The left coronary artery divides into the left anterior descending and circumflex arteries, which perfuse the left ventricle. A, Anterior view. B, Posterior view.
TABLE 17.2
| Areas Supplied by the Coronary Arteries | |
| Artery | Area Supplied |
| Right coronary | Right atrium (55% of persons) Right ventricle Intraventricular septum Sinus node (55% of persons) Atrioventricular node Bundle of His |
| Left anterior descending | Right atrium (45% of persons) Right ventricle (minor) Left ventricle (anterior, apex) Anterior papillary muscles Right and left bundle branches Intraventricular septum |
| Left circumflex | Left atrium Left ventricle (posterior, anterior) Sinus node (45% of persons) |
FIG 17.10 Venous drainage of the heart. Coronary veins drain blood from the myocardial capillary bed and deliver it into the right atrium.
Regulation of Coronary Blood Flow
Blood flow through coronary vessels is determined by the same physical principles that govern flow through other vessels of the body, namely driving pressure and vascular resistance to flow. According to Ohm’s law, an increase in driving pressure (P) increases blood flow (Q), whereas an increase in resistance (R) reduces blood flow: Q = P/R (see Chapter 15). Driving pressure through the coronary arteries is determined by aortic blood pressure and right atrial pressure. This relationship can be expressed in the following equation:
where ABP is aortic blood pressure and RAP is right atrial pressure. Thus an increase in aortic pressure enhances coronary blood flow, whereas an increase in right atrial pressure opposes coronary flow.
Coronary vascular resistance (R) has two major determinants: (1) coronary artery diameter and (2) the varying degrees of external compression attributable to myocardial contraction and relaxation. Coronary artery diameter is continuously adjusted to maintain blood flow at a level adequate for myocardial demands. Autoregulation is the term used to describe the intrinsic ability of the arteries to adjust blood flow according to tissue needs. Vessel dilation (vasodilation) occurs in response to increased tissue metabolism or reduced driving pressure, whereas decreased metabolic activity or increased driving pressure results in a decreased vessel diameter (vasoconstriction).
The mechanism of autoregulation can be explained by the metabolic hypothesis, which proposes that increased metabolism, reduced oxygen concentration, or decreased blood flow results in a buildup of vasodilatory chemicals in the vessel. Smooth muscle encircling the vessel relaxes in response to the presence of the chemicals, increasing vessel diameter. Several vasodilating substances have been proposed, including potassium ions, hydrogen ions, carbon dioxide, nitric oxide, prostaglandins, and adenosine. The endothelial cells that line vessels are known to secrete a variety of relaxing and constricting factors, which may contribute to autoregulation. Vasodilatory substances are washed away as blood flow increases in response to increased vessel diameter. A declining level of vasodilatory chemicals results in vasoconstriction. Thus vessel diameter is continuously adjusted according to concentrations of vasodilatory chemicals, which are directly related to the tissue’s metabolic activity.
One mechanism for autoregulation of coronary blood flow involves an adenosine triphosphate (ATP)–sensitive potassium channel in vascular smooth muscle. When ATP levels rise in response to increased coronary flow, the channel closes, making it easier to depolarize the cell and contract vascular smooth muscle. Contraction of vascular smooth muscle reduces the diameter of the coronary arteries and reduces blood flow. The opposite also occurs: a reduction in ATP level, due to low flow or increased metabolism, opens the K+ channels. Potassium then leaks out of the vascular smooth muscle and short-circuits the depolarizing influences. This inhibits vascular contraction, leading to vasodilation and increased coronary blood flow. Adenosine also contributes to regulation of the ATP-sensitive K+ channels, causing vasodilation when adenosine levels are elevated.
Nitric oxide (NO) produced by endothelial cells lining the coronary arteries is an important regulator of coronary blood flow. NO is a diffusible gas produced by the enzyme inducible nitric oxide synthase in response to numerous stimuli, including hypoxemia and platelet factors. NO is a potent vasodilator, and inhibition of its production is associated with reduced coronary blood flow. Many known risk factors for coronary heart disease have been shown to impair NO-dependent vasodilation of coronary arteries.
Vessel diameter also is regulated by the autonomic nervous system. The coronary arteries are primarily innervated by sympathetic nerves, but they also receive a small amount of parasympathetic innervation. The sympathetic neurotransmitter norepinephrine (NE) binds to both α1 and β2 receptors in coronary arteries; α1 stimulation results in vasoconstriction, whereas β2 stimulation dilates. Under normal conditions the vasodilator response predominates, but in pathologic states, excessive α1-mediated constriction can occur. The increased metabolic activity associated with sympathetic nervous system stimulation generally causes autoregulatory vasodilation and overrides the direct effect of NE on the vessels. Parasympathetic activity contributes to vasodilation by promoting the production of NO by coronary endothelial cells.
In addition to vessel diameter, coronary resistance is affected by myocardial contraction. During systole, cardiac muscle compression creates a marked rise in coronary resistance that reduces coronary blood flow (perfusion). Blood flow to the left ventricle is greatly decreased during systole because of the pressures generated by the thick muscular layer. Blood vessels that penetrate the myocardium to supply the innermost endocardial areas are more compressed during contraction than are outer epicardial vessels. Even though coronary artery driving pressure is greatest during ventricular systole, little blood flow reaches the left ventricle because of the high external pressure applied to the coronary vessels as the myocardium contracts. Therefore most myocardial blood flow occurs during the diastolic interval between ventricular contractions. The time the heart spends in diastole is directly related to heart rate. Faster heart rates reduce diastolic time and decrease coronary artery blood flow.
Cardiac muscle needs a continuous supply of oxygen and nutrients to perform its pumping functions. A disruption in cardiac blood flow (ischemia) generally results in some degree of pump failure and damage to cardiac tissues. Myocardial ischemia may be caused by conditions that reduce coronary blood flow or increase myocardial demands for oxygen. These include (1) reduced driving pressure (e.g., low aortic blood pressure or high right atrial pressure), (2) reduced vessel diameter (e.g., myocardial hypertrophy, arteriosclerosis, thrombosis, vasoconstricting chemicals), (3) reduced perfusion time (e.g., high heart rates, some dysrhythmias), and (4) increased metabolic demands (e.g., fever, sepsis, anemia).
Key Points
Cardiac Myocytes
Cardiac muscle cells are divided into two general types: working cells, which have primarily mechanical pumping functions; and electrical cells, which primarily transmit electrical impulses. Both types are excitable: they are able to produce and transmit action potentials. Working myocardial cells are packed with contractile filaments and compose the bulk of the atrial and ventricular muscle. Electrical cells function to initiate and coordinate contraction of the working cells. Differentiated cardiac myocytes are unable to enter the cell cycle to proliferate; however, they can increase in size and synthesize more contractile proteins (hypertrophy). New myocardial cells can be formed from stem cells that have the potential to divide. Stem cells may be recruited from the circulation and stimulated to divide and mature into myocytes within the myocardium. Conditions that increase myocardial cell death are thought to stimulate recruitment of stem cells into the myocardium. A high turnover rate of cardiac myocytes occurs and increases with age, suggesting that the entire population of cells within the heart is completely replaced 11 to 15 times over a lifetime. When the rate of myocardial cell loss exceeds replacement by stem cells, the condition of heart failure may ensue (see Chapter 19).
Myocyte Structure
Typical myocardial cells (myocytes) are illustrated in Fig. 17.11. Cardiac myocytes are described as muscle “fibers” because of their long, narrow shape. The plasma membrane (sarcolemma) of one cardiac cell is joined end to end with its neighbors by intercalated disks, which contain gap junctions that allow the rapid passage of electrical impulses from one cell to the next. The intercalated disks permit the many separate cells of the myocardium to function together in a coordinated manner. This arrangement is called a functional syncytium. The sarcolemma also forms membrane-lined channels that penetrate the cell and become the transverse tubules (T tubules) (Fig. 17.12). The T tubules permit extracellular fluid and ions to diffuse near intracellular structures. Movement of ions across the sarcolemma is an essential part of cellular excitation and the subsequent contraction of intracellular elements. Cellular contractile elements are simultaneously activated because signals at the cell surface are rapidly transmitted internally by the T tubules.
FIG 17.11 Myocardial cells, showing long narrow shape and interconnecting junctions, forming a functional syncytium. The end of one muscle cell is fused to the next by intercalated disks. Within these connections are specialized proteins that form a fluid-filled pore (gap junction) between the fused cells. Ions can travel through the gap junctions to transport changes in membrane potential from one cell to the next.
FIG 17.12 A, Schematic diagram of a portion of a cardiac myocyte showing the transverse tubules (T tubules), which extend at right angles from the plasma membrane (sarcolemma) into the cell interior. The T tubules are extensions of the plasma membrane that bring the extracellular fluid into juxtaposition with the terminal ends of the sarcoplasmic reticulum (SR). The T tubule with the SR on either side of it is called the triad of the reticulum. B, Calcium ions that enter the cytoplasm through voltage-gated L-type channels on the T-tubule membrane interact with the ryanodine receptors on the sarcoplasmic reticulum. The activated ryanodine receptors allow calcium ions to flow into the cell cytoplasm where they initiate contraction. As soon as they are released, calcium ions are rapidly captured by the sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA) pumps on the SR membrane.
The sarcoplasmic reticulum (SR) is an extensive labyrinth of hollow membrane that stores significant amounts of intracellular calcium. It contains Ca2+-sensitive channels that open briefly during depolarization and allow calcium ions to flow into the cytoplasm. An action potential traveling along the T tubule opens voltage-sensitive calcium ion channels (L type) in the plasma membrane. The Ca2+ ions that enter the cell through these channels interact with receptors on the SR membrane called ryanodine receptors (see Fig. 17.12B). Activation of these receptors opens calcium gates on the SR, and Ca2+ rushes into the cytoplasm to initiate contraction. The SR also contains powerful sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA) pumps that recover calcium ions from the cytoplasm and return them to the SR. Inside the SR, calcium is bound to specialized proteins, including calsequestrin. This helps keep the free calcium concentration in the SR lower such that the calcium transporters have a lower gradient to pump against.
Cardiac muscle cells are packed with numerous mitochondria that are strategically positioned along the contractile fibers of the cell. The heart is also endowed with an extensive capillary network, approximately one capillary per muscle cell. The large number of mitochondria and abundant oxygen supply are necessary to keep pace with the high ATP requirements of the contractile elements and ion pumps.
Structure of the Contractile Apparatus
Microscopic inspection of the cardiac myocyte reveals a typical pattern of banding called striation. This striated appearance is due to an organized structure of the proteins (myofibrils) of the contractile apparatus (Fig. 17.13). The contractile proteins, actin and myosin, are called filaments because they are long and narrow. Myosin filaments are larger and are referred to as thick filaments. Thin filaments are actually composed of several different types of protein bundled together. Actin is the primary constituent of thin filaments, with smaller amounts of the proteins tropomyosin and troponin bound to it.
FIG 17.13 Electron micrograph of muscle fibrils showing characteristic banding pattern. The dark vertical lines are the Z disks. A sarcomere extends from one Z disk to the next. Compare with the schematic drawing in Fig. 17.14. (From Fawcett DW: The cell, Philadelphia, 1981, Saunders.)
The thick and thin filaments are specifically arranged in contractile units called sarcomeres (Fig. 17.14). Sarcomeres are defined by dark bands called Z disks (also called Z lines), which lie perpendicular to actin and myosin filaments. A sarcomere extends from one Z disk to the next. Thin actin filaments are attached to Z disks and extend from them. The I bands (isotropic) are light in color and correspond to the position of thin actin filaments extending in both directions from the Z disk. Thick myosin filaments lie parallel to and between the thin filaments. They are held in place by a very large and elastic protein called titin that extends from the Z disk to the center of the sarcomere. Each myosin filament is surrounded by six thin filaments (see Fig. 17.14). An efficient, synchronized contraction is enhanced by this precise arrangement of contractile elements.
FIG 17.14 Thick and thin filaments are organized into contractile units called sarcomeres. A sarcomere extends from one Z disk to the next and represents the fundamental unit of muscle contraction. See text for description of bands, zones, and lines. Overlap of thick and thin filaments in each area is shown in cross-section at the bottom. Each thick filament interacts with six thin filaments that surround it.
Characteristics of Contractile Filaments
Myosin molecules are composed of six polypeptide chains: two heavy (H) chains and four light (L) chains. These light and heavy chains are organized into a tail region and two globular “head” areas (Fig. 17.15). The myosin heads interact with actin filaments to produce muscle contraction. Thick filaments consist of many myosin molecules with tail regions bundled together and heads protruding at intervals along the bundle. The head regions are flexible and can bend and pull on actin filaments to accomplish muscle contraction. Myosin heads are oriented in opposite directions on either side of the center tail region (see Fig. 17.15). Myosin heads have enzymatic properties and can cleave ATP to release the energy necessary for muscle contraction. Different forms of myosin have varying rates of ATP hydrolysis, which affects how quickly the muscle contracts. The serum level of thyroid hormone is known to affect the type of myosin produced in heart cells. Hyperthyroidism is associated with a fast-cycling type of myosin and hypothyroidism with a slow type of myosin. The rate of myosin cycling can also be regulated at the light chain of the myosin protein. Cellular enzymes that attach a phosphate to the light chain accelerate the rate of cycling. Phosphorylation is increased by activation of myocardial β1 receptors and enhances contractility.
FIG 17.15 Thick filament of the sarcomere is composed of myosin proteins. Myosin head groups are oriented in opposite directions on either side of the center tail region. Phosphorylation (P) of the regulatory light chain increases myosin activity and rate of cross-bridge cycling.
Thin filaments are composed of several different proteins, including actin, nebulin, tropomyosin, and troponin. Actin filaments are actually polymers of many globular actin proteins that are attached end to end, like two strings of beads, and then twisted together to form a helix (Fig. 17.16). Each of the actin beads has a site that can bind with myosin heads. Nebulin is a long protein that extends the entire length of the thin filament and is thought to regulate the length of the actin polymer such that all of the thin filaments are the same size. Tropomyosins are long, slender proteins that bind to a string of six or seven actin beads. When myocardial muscle is relaxed, tropomyosin molecules inhibit the myosin-binding sites on the actin beads. A third protein complex, troponin, is attached to the thin filament and regulates the availability of binding sites on the actin filament by controlling the position of tropomyosin. Each troponin is composed of three subunits, called troponins T, I, and C. Troponin T binds to tropomyosin, troponin I participates in the inhibitory actions of tropomyosin, and troponin C binds up to four molecules of Ca2+. As described in the following section, tropomyosin and troponin are important regulatory proteins that control the activities of actin and myosin filaments. The specific isoforms (amino acid sequences) of troponins T and I present in heart tissue differ from those in other types of cells, and their presence in the serum can be used to detect myocardial infarction (see Chapter 18).
FIG 17.16 Schematic drawing of the proteins that comprise the thin filament. A, Globular actin proteins combine to form long double-helix filaments. B, Nebulin (nebulette) is a long cytoskeletal protein that extends the length of the thin filament and is thought to regulate filament length. C and D, The proteins troponin and tropomyosin combine with the actin helix to form the thin filament.
Key Points
Molecular Basis of Contraction
Overview of Contraction
The heart’s pumping action is accomplished by the additive contractions of the many myocytes that form the cardiac chambers. Because each myocyte contributes only a small amount to overall muscle shortening, all cells of the chamber must shorten simultaneously to produce a forceful contraction. The specialized cells of the conduction system function to stimulate myocardial contraction in a coordinated way. An action potential traveling down the conduction system is the usual trigger for contraction. Cardiac myocyte depolarization causes ion channels in the plasma membrane and T tubules to open, permitting sodium and calcium entry and release of calcium from the SR. The presence of free calcium in the sarcoplasm (muscle cytoplasm) results in contraction. These events describe the process of excitation-contraction coupling.
Sliding Filament/Cross-Bridge Theory of Muscle Contraction
The sliding filament, or cross-bridge, theory of muscle contraction is suggested by the anatomic configuration of the sarcomere described earlier. Muscle shortening is accomplished by increasing the amount of overlap of actin and myosin filaments. The Z disks at the ends of the sarcomere move closer together as overlapping actin and myosin filaments pull past one another. Myosin heads grip binding sites on the actin beads and pull the thin filaments toward the sarcomere’s center. Each time a myosin head binds an actin bead, it forms a so-called cross-bridge. Flexible myosin heads move in a ratchetlike manner to tug on the actin filaments (Fig. 17.17). Each ratcheting motion moves actin filaments only minutely, and many sequential cross-bridge formations are required to shorten the entire sarcomere. Thus myosin heads bend back and forth, binding and pulling on the actin filaments in a steplike fashion. Actin filaments are prevented from slipping back to their original position because some myosin–actin bonds are forming while others are disengaging. The making and the subsequent breaking of each actin–myosin cross-bridge requires one molecule of ATP. Consequently, tremendous quantities of ATP are hydrolyzed with each cardiac contraction.
FIG 17.17 Cross-bridge cycle of muscle contraction. A, The myosin head has hydrolyzed its bound adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and inorganic phosphate (Pi), which remain on the myosin. In this state the myosin has high affinity for actin but cannot bind because the actin-binding sites are not accessible. B, When calcium ions enter the cell and bind to troponin, the tropomyosin-blocking protein moves to allow myosin to bind actin, forming a cross-bridge. C, The act of binding changes the shape of myosin so that ADP and Pi are released. The “power stroke” is accomplished by movement of the myosin neck region. D, When a new molecule of ATP binds to the myosin, it changes to a low-affinity state and releases from the actin. ATP is again hydrolyzed to ADP and Pi to restart the cycle. Each cross-bridge cycle uses one ATP molecule.
ATP hydrolysis, which occurs at the myosin head region, provides the energy for contraction and affects the capability of myosin to bind actin. Myosin has two functional states or conformations: (1) a low-affinity state in which it binds weakly and (2) a high-affinity state in which it avidly binds actin. The affinity of the myosin head for actin depends on whether ATP is bound (low affinity) or ADP and inorganic phosphate (Pi) are bound (high affinity). A proposed sequence of cross-bridge cycling is as follows (see Fig. 17.17):
Continued cross-bridge cycling is dependent on the availability of ATP and calcium ions. A lack of ATP results in fewer cross-bridge cycles and inability of the muscle to shorten normally.
Role of Calcium in Muscle Contraction
Muscle contraction is dependent on the presence of an adequate amount of calcium ions in the cytoplasm. In the absence of free intracellular calcium, muscle contraction will not take place, even though myosin head groups have high affinity for actin-binding sites. This phenomenon can be explained in the following way. At rest, myosin heads are prevented from binding to actin by tropomyosin proteins, which inhibit actin-binding sites. The position of tropomyosin protein is controlled by troponin. When calcium is absent, troponin induces tropomyosin to inhibit the actin-binding sites. When calcium binds to troponin C, the troponin complex induces tropomyosin to move and expose the binding sites (see Fig. 17.17A and B). Cross-bridge formation immediately ensues because myosin heads have high affinity for these sites in the relaxed state. The concentration of free calcium ions in the myocardial cell determines how many actin sites are exposed and for how long and therefore determines the number of cross-bridges and extent of contraction. The release of Ca2+ into the cytoplasm is regulated by numerous neurotransmitters and hormones that affect contractility as described in later sections of this chapter.
Energy of Muscle Relaxation
Although muscle relaxation is generally viewed as a passive phenomenon, it actually requires significant energy to pump calcium ions out of the cytoplasm. As calcium levels fall, calcium diffuses away from the troponin molecules and tropomyosin is induced to cover the actin-binding sites. With actin-binding sites covered, myosin heads are unable to initiate cross-bridge formation, and thick and thin filaments slide back to their resting positions. Removal of calcium ions is an energy-requiring process. Membrane pumps located in the sarcolemma and SR actively move calcium out of the sarcoplasm against a concentration gradient (Fig. 17.18). The sarcolemma contains two different calcium pumps: one that requires ATP and one that uses the potential energy of the sodium gradient to remove calcium from the cell (3 Na+ for 1 Ca2+). Calcium pumps on the SR (SERCAs) require ATP. Thus energy deficiency attributable to myocardial ischemia can impair diastolic relaxation as well as systolic contraction of the heart muscle.
FIG 17.18 Calcium ions (Ca2+) are removed from the cardiac muscle cell cytoplasm by energy-dependent protein transporters in the plasma membrane and sarcoplasmic reticulum (SR) membrane. Thus cardiac relaxation is an energy-requiring process. ADP, Adenosine diphosphate; ATP, adenosine triphosphate; Pi, inorganic phosphate.
Key Points
Cardiac Energy Metabolism
The heart, like other tissues in the body, utilizes energy from ATP hydrolysis to drive its energy-requiring functions. Synthesis of ATP in cardiac muscle cells is accomplished by the same glycolytic and oxidative reactions described in detail in Chapter 3.
Oxygen Utilization
Because the heart is continuously active, its energy requirements are considerable. Very little ATP is stored in myocardial cells, so a continuous supply of oxygen and nutrients is necessary to support ongoing ATP synthesis. Even under normal resting conditions, the heart extracts a large portion of oxygen from the blood perfusing it. Therefore conditions of increased oxygen demand must be met by increasing the rate of coronary blood flow. When oxygen delivery is insufficient to meet requirements for oxidative phosphorylation, the cell must rely on ATP produced by glycolysis. Unfortunately, glycolysis results in production of only enough ATP to maintain the cell for seconds to minutes. In addition, anaerobic glycolysis results in local buildup of lactic acid, which may further impair cardiac performance.
Under conditions of relative ATP excess, myocardial cells are able to transfer energy to a storage form called creatine phosphate (CP). This transfer is accomplished by the enzyme creatine kinase (CK or CPK), in the following reaction:
Although amounts of cellular CP are limited, they provide an immediate source of energy when cellular ATP levels drop acutely. Under conditions of ischemia, the enzymatic reaction would proceed in reverse, utilizing CP and adenosine diphosphate (ADP) to produce ATP for immediate use by the cell. This phosphate transfer reaction is important during fluctuations in ATP supply because it does not require the presence of oxygen.
The enzyme CK is also useful in the diagnosis of myocardial cell damage. Myocardial cells that lose membrane integrity (necrosis) leak their enzymes into extracellular fluid and eventually into the bloodstream. Elevated levels of blood CK are indicative of the degree of acute myocardial cell death. Different types of tissue contain different forms of CK (isoenzymes). The myocardial band (MB) form of CK is found in cardiac muscle, and elevated serum levels of this enzyme are indicative of myocardial infarction. Other intracellular proteins, including troponin and myoglobin, are released during myocardial cell death and can be used as markers of myocardial infarction (see Chapter 18).
Substrate Utilization
The primary foodstuffs that provide fuel for energy-producing enzymatic processes in cardiac muscle are glucose and fatty acids. Amino acids are less important metabolic substrates for cardiac muscle except during states of starvation. The amount of fatty acids and glucose utilized by heart muscle cells depends on their relative concentrations in the blood. Fatty acids are the preferred fuel, particularly in a fasting state, when glucose levels are lower. Under fasting conditions, fatty acids account for approximately 85% of myocardial fuel, and glucose contributes only 15%. After eating, when blood glucose levels rise, glucose utilization may increase to about 50%. Fatty acid metabolism requires oxygen and is therefore not useful under conditions of ischemia. The heart is also able to use lactate and ketones as sources of energy when they accumulate in the circulation. Lactate is derived from pyruvate under conditions of anaerobic metabolism, whereas ketones are formed from lipid metabolism when carbohydrate supplies are low. Thus the heart is equipped to use a variety of substrates to produce ATP under varying metabolic conditions.
Key Points
Cardiac Electrophysiology
The plasma membranes of cardiac cells are endowed with special ion channels that make the cells excitable. Excitable tissues are capable of generating and conducting action potentials. The heart is rhythmically activated by action potentials, which are generated and transmitted by a specialized conduction system. Spread of an action potential over cardiac muscle cell surfaces results in myocardial contraction. An understanding of the electrophysiologic properties of the heart is important because many cardiac disorders result in disturbances in electrical function that produce abnormal conduction pathways, dysrhythmias, and conduction blocks.
Cardiac Resting Potential
Like other cells, resting cardiac cells are negatively charged on the inside with respect to the outside (see Chapter 3). A difference in potassium ion concentration across the cell membrane is the primary determinant of the resting membrane potential. Atrial and ventricular muscle cells generally have a resting membrane potential of −85 to −95 mV. Pacemaker cells in the SA node are less polarized, having a resting membrane potential of about −60 mV. An increase in the concentration of extracellular potassium ion tends to hypopolarize the cell (make it less negative), and a lower-than-normal extracellular potassium concentration tends to hyperpolarize the cell (make it more negative). The degree of polarization is an important determinant of the ease with which an action potential can be initiated. Abnormalities in serum potassium level are a common source of cardiac dysrhythmias.
Cardiac Action Potential
Depolarization of cardiac cells to a threshold point results in activation of voltage-sensitive ion channels in the membrane. A myocardial action potential (Fig. 17.19) results from movement of ions through these open voltage-gated channels. The action potential in atrial and ventricular cells has five characteristic phases. Atrial action potentials are shorter in duration because they have a reduced phase 2 compared with ventricular cells.
FIG 17.19 The ventricular myocardial action potential has five characteristic phases, representing changes in ion movement through the plasma membrane. Phase 0: Rapid upstroke attributable to sodium influx. Phase 1: Slight repolarization attributable to closure of sodium channels and initiation of potassium efflux. Phase 2: Plateau attributable to offsetting influx of calcium and efflux of potassium. Phase 3: Rapid repolarization attributable to closure of calcium channels and increased potassium efflux. Phase 4: Resting membrane potential reestablished attributable to closure of all voltage-sensitive channels.
Phase 0
Phase 0 begins when the membrane potential approaches threshold and voltage-gated “fast” sodium channels open momentarily. As a result of a steep electrochemical gradient for sodium entry, rapid influx of sodium ions occurs. Sodium entry depolarizes the cell by neutralizing the difference in charge (polarity) across the membrane. A steep depolarizing deflection (upstroke) is recorded. Class I antidysrhythmic agents such as quinidine and lidocaine block voltage-gated sodium channels and interfere with phase 0 depolarization (see Chapter 19).
Phase 1
Phase 1 is identified as a small repolarizing deflection that corresponds to closure of the fast sodium channels and transient efflux of potassium from the cell through K+ channels. The interior of the cell is now more positively charged than at rest, which induces potassium ions to leave the cell.
Phase 2
Phase 2 is also called the plateau phase because little change in membrane potential occurs during this time, even though ions continue to move across the membrane. Phase 2 is primarily associated with an influx of calcium ions, which is offset by an efflux of potassium ions. The ability of K+ to leave the cell down its electrochemical gradient is inhibited during the plateau phase by a relative inhibition of a subset of potassium channels. This is sometimes called potassium rectification. Chloride also may leave the cell during this phase. The voltage-gated calcium channels open and close slowly in comparison to fast sodium channels and are thus referred to as slow channels or L-type channels (long-lasting).
The calcium that enters the cell during phase 2 is linked to muscle contraction as previously described. The L-type calcium channels can be modified by agonists that prolong the open phase, such as catecholamines, and by antagonists that shorten the open phase, such as acetylcholine. Calcium channel–blocking agents (class IV antidysrhythmic agents) are used commonly in patients with cardiovascular diseases to inhibit calcium influx. β-Blockers (class II antidysrhythmics) also reduce calcium ion influx during phase 2 by indirectly inhibiting calcium channels.
Phase 3
Phase 3 is characterized by a rapid return to the resting membrane potential. This is accomplished by closure of the slow calcium channels and continued and even more rapid efflux of potassium ions from the cell through a variety of potassium channels. Sodium channels remain absolutely refractory during phases 1, 2, and early 3. The latter part of phase 3 represents a relative refractory period, when sodium channels may be induced to open, but a larger-than-normal depolarizing stimulus is required. If an abnormally early (premature) depolarization occurs during the relative refractory period, it will be conducted more slowly than usual because few fast Na+ channels are ready to be activated. Slow conduction through the myocardium predisposes to cardiac dysrhythmias, such as ventricular fibrillation (see Chapter 19). Class III antidysrhythmic agents, such as amiodarone, increase the refractory period by inhibiting opening of potassium channels during phase 3.
Phase 4
Phase 4 of the ventricular myocyte action potential corresponds to the period of time between action potentials when no changes in membrane voltage are evident and the resting membrane potential is present. The resting membrane potential in ventricular myocardial cells is flat, and they do not spontaneously depolarize. In contrast, cells in the pacemaker and conduction system automatically depolarize and have a sloping phase 4. The Na+–K+ pumps and Ca2+ pumps work continuously throughout all phases to reestablish the internal and external concentrations of sodium, potassium, and calcium ions.
Rhythmicity of Myocardial Cells
Rhythmicity and automaticity refer to regular, spontaneous generation of action potentials. Rhythmic pacemaker cells have a recognizable action potential that is characterized by a sloping phase 4 (Fig. 17.20), in contrast to the flat phase 4 of ventricular muscle cells. A requirement for rhythmicity is that the cell membrane has channels that automatically open during phase 4. These channels begin to open as the membrane potential becomes more negative during the repolarization phase. Progressive channel opening makes the pacemaker cells leaky to Na+, Ca2+, and K+. Gradually the flow of positive ions into a cell offsets the repolarizing currents and depolarizes the membrane, resulting in generation of an action potential. One contributor to the automatic depolarization during phase 4 is the If channel. The If channels originally were named for a “funny” current and later discovered to be sodium channels that are activated by membrane repolarization. Channels that allow calcium and potassium leakage are also operative during phase 4 in pacemaker cells. Late in phase 4, an increase in calcium ion influx occurs through voltage-gated calcium channels called T type, for “transient.” These channels open and close more quickly than the L-type calcium channels that open during the action potential. Spontaneous release of Ca2+ from the SR also contributes to depolarization by activating the 3Na+/Ca2+ exchanger and promoting Na+ influx. Many of these channels can be regulated by various means, including autonomic neurotransmitters, in order to change heart rate. An action potential is initiated when phase 4 depolarization reaches the threshold for the opening of voltage-gated, L-type, slow calcium channels. Repolarization is achieved in large part by an exodus of potassium ions from the cell.
FIG 17.20 Rhythmic cells (A) have a sloping phase 4, in contrast to the flat phase 4 of the atrial (B) and ventricular (C) muscle cells. Spontaneous depolarization during phase 4 allows pacemaker cells to develop action potentials automatically. SA, Sinoatrial. (Adapted from Hoffman BF, Cranefield PF: Electrophysiology of the heart, New York, 1960, McGraw-Hill.)
The rate of rhythmic discharge is determined by the relative influx of Na+ and Ca2+ versus the efflux of K+. In a normal heart, a cell with the fastest rate of spontaneous depolarization becomes the pacemaker for the rest of the heart. Cells in the SA node, located in the right atrium, generally function as the heart’s pacemaker because they have the fastest rate of spontaneous depolarization. However, other cells in the conduction system are also capable of spontaneous depolarization and may initiate an action potential in certain circumstances.
The steepness of the slope of phase 4 depolarization determines the rate of action potential generation and therefore heart rate. Several factors determine the steepness of the slope, including membrane permeability to sodium, calcium, and potassium. For example, an increase in potassium ions leaving the cell would slow depolarization and result in a slower rate. Rhythmicity may be influenced by the autonomic nervous system, drugs, and electrolyte balance. These conditions are discussed in the following sections.
Specialized Conduction System of the Heart
Some myocardial cells are specialized to conduct action potentials throughout the heart in an organized and rapid manner. These cells constitute the conduction system of the heart, as shown in Fig. 17.21. Normal excitation of the heart follows a pathway beginning with the SA node, atrial internodal pathways, AV node, bundle of His, ventricular bundle branches, and, finally, Purkinje fibers.
FIG 17.21 Schematic drawing of the conduction system of the heart. An impulse normally is generated in the sinus node and travels through the atria to the AV node, down the bundle of His and Purkinje fibers, and to the ventricular myocardium. Recording of the depolarizing and repolarizing currents in the heart with electrodes on the surface of the body produces characteristic waveforms.
The SA node is located in the right atrium near the superior vena cava inlet. It receives innervation from sympathetic and parasympathetic branches of the autonomic nervous system. The SA node generally serves as a pacemaker for the heart, generating about 70 (range, 60 to 100) action potentials per minute in a resting adult. SA action potentials are spread contiguously through gap junctions to adjacent atrial cells at a fast rate. A fibrous skeleton separates atria from ventricles and prevents the spread of impulses from atrial cells to ventricular cells. Several small bundles of atrial muscle cells conduct impulses slightly faster than the usual atrial cell. One such bundle, the anterior interatrial band (Bachmann bundle), conducts impulses from the SA node to the left atrium. Atrial depolarization results in atrial contraction, which increases the volume of blood delivered to the still-relaxed ventricular chambers.
After traversing the atria, the impulse initiated at the SA node arrives at the AV node (AV junction) located in the posterior septal wall of the right atrium just behind the tricuspid valve. There is a characteristic slowing of impulse conduction through the AV node, which allows for completion of atrial contraction before initiation of ventricular systole. The AV node is actually composed of different types of fibers that have somewhat different action potential conduction times. Overall, it normally takes about 0.13 second for an impulse to pass through the AV node. The AV node is richly innervated by the autonomic nervous system. The AV node spontaneously depolarizes at a rate of 40 to 60 times per minute and usually becomes the heart’s pacemaker if the SA node fails.
Purkinje cells (fibers), which lead from the AV node to ventricular myocardium, are vastly different from AV nodal cells. They are large and well structured to conduct impulses very rapidly. After penetrating the AV fibrous barrier, the bundle of Purkinje fibers travels 5 to 15 mm down the intraventricular septum toward the apex. The main bundle then divides into left and right bundle branches, which travel down the left and right sides of the intraventricular septum. Successive branches of Purkinje fibers penetrate the ventricular muscle mass from the endocardial side. Intraventricular septal areas are depolarized first, followed by apical muscle, and finally the lateral walls. Early septal depolarization allows the septum to contract first and provide a stable wall against which the left and right ventricles can contract. The total time elapsed between main bundle branch and terminal Purkinje fiber depolarization is only 0.03 second. Therefore the entire ventricular endocardium is activated almost simultaneously. Purkinje fibers are capable of spontaneous depolarization at a rate of 15 to 40 times per minute and may become pacemakers for the heart if impulses from the SA and AV nodes are interrupted.
Action potentials are rapidly transmitted from the terminal Purkinje fibers to cardiac muscle fibers and then spread contiguously from cell to cell through gap junctions in the ventricular muscle. Approximately 0.03 second is required for the impulse to be transmitted through the ventricular myocardium. Impulses normally travel from the terminations of Purkinje fibers at endocardial surfaces toward the epicardial surfaces. Depolarization of the right ventricle is accomplished slightly sooner than the left because of differences in muscle mass. Depolarization of the ventricular myocardium is followed by contraction and ejection of blood from the ventricles.
The capability of faster pacemakers to suppress the automatic discharge of slower pacemakers is called overdrive suppression. A slower pacemaker may be revealed if the normal pacemaker is suddenly interrupted. Sometimes it takes time for the slower pacemaker to “kick in” and begin pacing at its intrinsic rate. A previously rapid rate of depolarization apparently enhances the activity of membrane Na+–K+ pumps, resulting in a period of hyperpolarization (more negative resting potential) when the faster pacemaker suddenly stops. Thus it takes slightly longer to reach threshold and initiate the first action potential.
Autonomic Regulation of Rhythmicity
Both sympathetic and parasympathetic nerves supply the heart. Sympathetic innervation is widespread to all areas, including the ventricular myocardium. Parasympathetic innervation, by way of the vagus nerves, is localized primarily in SA and AV nodal areas. The right vagus nerve supplies the SA node, whereas the left vagus nerve supplies the AV node. The autonomic nervous system exerts control over heart rate and velocity of impulse conduction. In general, sympathetic activation increases heart rate (chronotropic effect) and increases speed of conduction (dromotropic effect), as well as inducing heart muscle to contract more forcefully (inotropic effect) and relax more quickly (lusitropic effect). These effects are achieved by release of NE from sympathetic nerve endings. Binding of NE to β receptors on heart muscle cell membranes increases production of cAMP, which regulates several membrane channels and pumps and increases depolarizing ion currents.
Parasympathetic stimulation primarily results in a reduction in heart rate and speed of action potential conduction. Acetylcholine is the neurotransmitter released by parasympathetic nerve endings. Acetylcholine binding to muscarinic receptors on heart cells inhibits cAMP production and increases membrane permeability to potassium ions, allowing them to leak from the cell. The resulting hyperpolarization makes it more difficult to reach threshold and initiate an action potential. The resting heart is normally under a predominant parasympathetic influence, which results in an SA discharge rate of about 70 beats/min. If parasympathetic activity is blocked, the spontaneous discharge rate of SA nodal cells increases to about 100 beats/min. An increase in vagal activity can reduce heart rate significantly. Breath holding, bearing down during defecation, and pressing on the carotid arteries may increase vagal tone and reduce heart rate. This is sometimes called a vasovagal response and may lead to dizziness and fainting.
Key Points
Electrocardiography
As action potentials spread from cell to cell throughout the myocardium, an electrical current is transmitted to the body surface and can be detected by electrodes placed on the skin. A recording of these electrical currents is called an electrocardiogram (ECG). The ECG is a useful indicator of abnormalities of the heart’s conduction system. Irregularities in initiation of impulses, conduction rates, and conduction pathways can be identified. The ECG has a different appearance from the cardiac action potential described previously because it registers depolarizing and repolarizing currents in the whole heart rather than the activity of individual myocytes (Fig. 17.22).
FIG 17.22 Comparison of the action potential from a single ventricular muscle cell, showing rapid depolarization and prolonged repolarization phases, against an electrocardiogram of potentials from the heart as a whole. Ventricular myocytes remain depolarized and refractory throughout the entire QT interval.
Electrical currents traveling through the heart have both direction and magnitude and are often described as vectors. At any instant, electrical currents are moving in various directions through different regions of the heart. Waveforms recorded at the ECG electrodes are algebraic sums of all of these vectors. Patterns of electrical activity shown on the ECG vary according to the placement of electrodes on the body. In general, a wave of depolarization moving toward a positive recording electrode will register as an upward deflection on the ECG. A wave of repolarization moving away from a positive electrode also will register as an upward deflection on the ECG. A downward deflection results from a wave of depolarization moving away from a positive electrode (Fig. 17.23). Placement of a recording electrode on the lower-left extremity (lead II) results in the typical ECG pattern shown in Fig. 17.24. A description of the usual electrode placements is included in the section “Tests of Cardiac Function” at the end of this chapter.
FIG 17.23 Electrocardiographic waveforms may be positive (upward) or negative (downward), depending on the location of electrodes on the chest. A, A wave of depolarization moving toward a positive electrode results in a positive deflection. B, A wave of repolarization moving away from a positive electrode results in a positive deflection. C, A wave of depolarization moving away from a positive electrode results in a negative deflection.
FIG 17.24 Usual electrocardiographic pattern recorded from lead II, showing characteristic waves and intervals.
Each deflection on the ECG has a normal characteristic shape and time interval (see Fig. 17.24). The three major wave complexes are the P wave, which corresponds to atrial depolarization; the QRS complex, which represents ventricular depolarization; and the T wave, which reflects ventricular repolarization. The PR interval, between the beginning of the P wave and the beginning of the QRS complex, includes atrial, AV node, and His–Purkinje fiber depolarization. The normal sequence of ventricular depolarization begins with the septum, followed by the apex, and finally the base of the ventricular walls. Septal depolarization begins on the left septal surface and then travels toward the right, resulting in a small negative deflection, the Q wave in lead II (Fig. 17.25). A large upright R wave corresponds to a wave of depolarization traveling down the ventricles toward the apex. Depolarization of the ventricular base, because it moves in a direction away from the lower limb electrode, is recorded as a negative S wave. The ST interval, between the S wave and the beginning of the T wave, is isoelectric (flat) because the entire ventricle is depolarized and no detectable current is flowing. The QT interval, from the beginning of the QRS complex to the end of the T wave, is commonly measured as an indicator of ventricular systole. The T wave is normally upright in lead II, representing a wave of repolarization moving away from a positive electrode. In some patients, particularly those with slow heart rates, the T wave is followed by a small positive deflection, called a U wave. Prominent U waves also are a sign of a low potassium level. Abnormalities in any time intervals may indicate abnormal conduction pathways and enhanced or slowed conduction times. Rhythm disturbances are discussed in detail in Chapter 19.
FIG 17.25 QRS complex results from the sequence of ventricular depolarization. A, In lead II, septal depolarization is in a direction away from the positive electrode, resulting in a negative Q wave. B, Depolarization of the apex of the heart is in a direction toward the positive electrode, resulting in a large positive R wave. C, Depolarization of the lateral walls and base of the ventricles is in a direction away from the positive electrode, resulting in a negative S wave.
Key Points
Determinants of Cardiac Output
Cardiac output is a measure of the amount of blood pumped out of the heart each minute. Because the heart’s primary function is to pump enough blood to circulate oxygen and nutrients to tissues, the cardiac output is an extremely important indicator of cardiovascular health. Normal resting cardiac output is approximately 5 to 6 L/min, but it varies with body size and age. Cardiac output is often indexed to body surface area in an attempt to adjust for these differences (cardiac index = cardiac output/body surface area). A normal cardiac index ranges from 2.8 to 3.3 L/min/m2. Regardless of the actual number of liters of blood pumped per minute, the adequacy of tissue perfusion is ultimately important.
Cardiac output is a product of heart rate and stroke volume (CO = HR × SV). Stroke volume refers to the amount of blood ejected from the ventricle with each contraction. An increase in heart rate (to a point) and/or an increase in stroke volume will result in a greater cardiac output. Conversely, a low heart rate and/or a decreased stroke volume will cause cardiac output to fall. To a certain extent, a change in one factor can be compensated for by a change in the other, thus maintaining cardiac output at a constant level. For example, it is common for an individual with limited stroke volume attributable to cardiac disease to have a high resting heart rate. Any physiologic, pharmacologic, or pathologic process that alters heart rate or stroke volume may affect cardiac output and therefore tissue perfusion.
Determinants of Heart Rate
Heart rate is primarily influenced by the autonomic nervous system. Release of NE by sympathetic nerve endings results in an increased heart rate. A similar effect results from circulating NE and epinephrine released from the adrenal gland during sympathetic stimulation. Sympathetic activation of the heart is regulated by several reflex pathways that constantly monitor blood pressure and metabolic activity in the body. In general, detection of inadequate blood pressure, a lack of oxygen, or a buildup of metabolic end products results in activation of the sympathetic nervous system. Specialized sensory nerve endings, called baroreceptors, located in the aortic arch and carotid arteries respond to changes in blood pressure and transmit this information to the central nervous system (CNS) by way of cranial nerves IX and X. A decline in blood pressure causes parasympathetic system inhibition and cardiac sympathetic nerve activation, resulting in a rise in heart rate. Conversely, a rise in blood pressure causes the heart rate to fall because of parasympathetic activation and sympathetic inhibition. Under normal resting conditions, the heart rate is under parasympathetic influence, with a usual rate of approximately 70 beats/min.
In addition to baroreceptors, other sensory fibers that detect pressure are located in the cardiac chambers. These sensory receptors respond to changes in intrachamber pressure, which reflect the volume of blood in the chamber. Atrial or ventricular overdistention suppresses parasympathetic influence and increases heart rate (Bainbridge reflex). Heart rate may also be influenced by higher CNS activities that do not involve reflex pathways. Anxiety, fear, stress, excitement, trauma, and fever may activate the sympathetic system, for example. A variety of drugs can mimic or block the effects of both sympathetic and parasympathetic systems and therefore influence heart rate (see Chapter 18).
In general, an increase in heart rate results in an increase in cardiac output; however, at very high heart rates, cardiac output may actually fall. At high heart rates (e.g., more than 200 beats/min in the young, even lower in the adult), the time for diastolic ventricular filling can be significantly reduced, resulting in a low stroke volume. The benefit of increased heart rate is therefore undermined by impaired pumping efficiency.
Determinants of Stroke Volume
Three major factors influence stroke volume: (1) the volume of blood in the heart (preload), (2) the contractile capabilities of heart muscle (contractility), and (3) the impedance opposing ejection of blood from the ventricle (afterload). Each of these factors is in turn influenced by many other physiologic, pharmacologic, and sometimes pathologic variables.
Volume of Blood in the Heart (Preload)
The heart can only pump as much blood as is delivered to it by the circulatory system. Blood returning to the heart from the circulation is often called venous return. Normally, venous return is equal to cardiac output because the circulatory system is just that—a circuit. However, there may be inequalities over several heartbeats when changes in blood volume or blood distribution occur. The heart is well suited to adjust to these beat-to-beat changes in venous return such that the healthy heart pumps essentially whatever amount is delivered to it.
The amount of blood present in the ventricles just before contraction (end-diastolic volume) is an important determinant of stroke volume. The relationship between diastolic volume and the force of myocardial contraction is known as the Frank–Starling law of the heart. In essence, this law states that an increase in resting muscle fiber length results in a greater development of muscle tension. Ventricular muscle fiber length is determined by the volume of blood it contains, commonly called the preload. An increase in preload results in a greater force of contraction and a larger stroke volume. In this way, the ventricle is able to adjust its stroke volume, beat by beat, according to the amount of blood to be pumped.
The Frank–Starling law of the heart (also called the length–tension relationship) may be understood by recalling the molecular structure of contractile units of heart muscle. For contraction to occur, the actin and myosin filaments that make up the sarcomere must form cross-bridges and slide together. Stretching the muscle before contraction is believed to optimize the space between the actin and myosin filaments, bringing them closer together and resulting in more cross-bridge formation (Fig. 17.26). Stretching the muscle before contraction also makes the contractile apparatus more sensitive to calcium ions such that a greater contractile force occurs for a given calcium concentration.
FIG 17.26 Force of muscle contraction depends in part on its resting length before activation. At optimal lengths, the greatest tension is developed, and cross-bridge formation is enhanced.
The cardiac function curve describes the effects of preload on ventricular stroke volume (Fig. 17.27). In practice, stroke volume and ventricular end-diastolic volume are difficult to measure, and other indicators, such as ventricular pressure and cardiac output, may be used. Cardiac function curves can be measured in persons with poorly functioning hearts to determine the best filling volume (preload) for optimizing cardiac output. Often, the failing heart requires a higher-than-normal preload to maintain a normal cardiac output. However, there are limits to the improvement in stroke volume with increased diastolic filling, and beyond that point the curve will flatten. On the flat part of the curve, an increase in preload increases the workload of the heart, but does not provide an improvement in output. The workload imposed on the heart chambers by preload is sometimes called the volume work of the heart. An increase in preload increases the volume work of the heart, which must be met by increased oxygen uptake to maintain adequate ATP production.
FIG 17.27 Cardiac function curves showing the dependence of ventricular stroke volume on preload. Different hearts have different cardiac function curves and may respond differently to the same degree of preload. PSNS, Parasympathetic nervous system; SNS, sympathetic nervous system.
Contractile Capabilities of the Heart (Contractility)
Heart muscle contractility depends on several factors, including (1) the amount of contractile proteins in the muscle cells, (2) the availability of ATP, and (3) the availability of free calcium ions in the cytoplasm. Contractility is, by definition, independent of fiber end-diastolic length and is therefore not affected by preload. Given an adequate ATP supply, the contractile state of the normal myocardium is primarily determined by factors that increase the availability of free calcium ions within the myocardial cell. In general, an increased intracellular free calcium level can be accomplished by enhanced release from internal stores, enhanced entry from extracellular fluid, and reduced rates of extrusion across the plasma membrane.
A variety of agents that increase contractility, called positive inotropes, are associated with increased intracellular calcium levels in the heart. These include the sympathetic neurotransmitters NE and epinephrine, thyroid hormone, caffeine, digitalis, and many others. Agents that depress contractility, called negative inotropes, achieve their effects by reducing intracellular calcium levels. These agents include L-type calcium channel blockers, parasympathomimetics, and sympathetic blocking drugs. The baroreceptor reflex, described previously in relation to heart rate, is also an important regulator of stroke volume through its effects on contractility. Positive inotropic agents increase ATP utilization by the myocardium, whereas negative inotropes decrease myocardial workload and reduce ATP requirements.
Cardiac disease may adversely affect contractility because of an inadequate oxygen supply or because of loss of myocardial pumping cells. These disorders are discussed in Chapter 18.
Impedance to Ejection From the Ventricle (Afterload)
The third major determinant of stroke volume is afterload, which refers to the impedance or resistance that must be overcome to eject blood from the chamber. Left ventricular afterload is determined primarily by aortic blood pressure. Because high blood pressure increases left ventricular afterload, vasodilating agents that reduce blood pressure can significantly decrease afterload. Normally the aortic valve offers little impedance to flow; however, aortic valve narrowing may significantly increase afterload. An increase in afterload will result in a decrease in stroke volume unless contractility or preload (or both) is adjusted to compensate. Conversely, a decrease in afterload will allow a larger-than-normal volume of blood to be ejected from the heart, requiring less myocardial work. The work done by the heart to overcome afterload is often called the pressure work of the heart. An increase in afterload increases pressure work and requires greater tension development within the walls of the chamber (wall stress). Increased wall stress not only increases myocardial workload and oxygen consumption but also, if prolonged, may trigger structural changes leading to hypertrophy of myocytes.
The ventricles normally eject about 60% to 70% of their end-diastolic volume during contraction; the remaining 30% to 40% remains in the ventricle. Ejection fraction is influenced by afterload as well as preload and contractile state. A reduced ejection fraction is a common finding in persons suffering from myocardial infarction. Ejection fractions less than 40% indicate significant myocardial impairment and may be associated with systolic heart failure (see Chapter 19).
Cardiac Workload
The oxygen requirements of the heart are related to the amount of energy (ATP) exerted to perform its pumping function. The four determinants of cardiac output described in the previous section—heart rate, preload, contractility, and afterload—are also the major determinants of cardiac energy requirements. An increase in any of these four factors will increase ATP requirements and therefore cardiac cell oxygen requirements. High afterload is most detrimental because it greatly increases cardiac work without producing a higher cardiac output. When oxygen supply to the heart is impaired, as in coronary atherosclerosis, it may be beneficial to reduce myocardial oxygen demand by reducing cardiac workload. This may be accomplished by reductions in heart rate, preload, afterload, and contractility.
Key Points
Endocrine Function of the Heart
In addition to its pumping function, the heart has an endocrine function: secretion of natriuretic peptides. Atrial natriuretic peptide (ANP) is synthesized by myocytes in the atria and released in response to atrial stretch. Increased atrial stretch occurs when blood volume becomes excessive. The ventricles produce a related peptide called B-type natriuretic peptide (BNP) when they are chronically overdistended. An elevated BNP value is a marker for congestive heart failure. ANP and BNP cause enhanced excretion of sodium and water by the kidney. In general, the effects of the natriuretic peptides are antagonistic to those of the renin–angiotensin–aldosterone system (see Chapter 26).
Tests of Cardiac Function
In addition to patient history, laboratory results, and physical assessment, a number of diagnostic tests may be employed to evaluate cardiac function. The ECG is routinely obtained and provides information about the heart’s conduction patterns. Echocardiography and nuclear cardiography are tests that use various modes to image the heart. A more direct assessment of cardiac function can be obtained by cardiac catheterization. In addition, a number of methods have been developed to quantify myocardial blood flow. Each of these studies is briefly described in this section.
Electrocardiography
The ECG graphically indicates electrical currents generated by cardiac cells. The current is registered by skin electrodes placed in particular positions on the body. The standard ECG has 12 different leads that are obtained through 10 skin electrodes: 3 standard bipolar limb leads, 3 augmented unipolar limb leads, and 6 unipolar chest leads. Bipolar leads represent a difference in electrical potential between two electrodes, one positive and one negative. Augmented unipolar limb leads represent a difference in potential between one electrode and the average of the other two limb electrodes. Unipolar chest leads represent a difference in potential between the chest electrode and a location at the center of the heart. Each lead provides a different ECG because of its particular “view” of current flow through the heart.
The three standard bipolar limb leads are lead I, lead II, and lead III (Fig. 17.28): lead I measures the current between the right arm and left arm, lead II measures the current between the right arm and left leg, and lead III measures the current between the left arm and left leg. A normal ECG from leads I, II, and III is illustrated in Fig. 17.29.
FIG 17.28 Positions of standard bipolar limb leads I, II, and III. The positive (+) lead is the recording lead.
FIG 17.29 Normal electrocardiogram recorded from the three standard bipolar limb leads. The R wave is normally upright in leads I, II, and III.
Electrode placement for the augmented unipolar limb leads is illustrated in Fig. 17.30. Unipolar limb lead electrodes provide the positive pole: lead aVR is recorded from the right arm, lead aVL is recorded from the left arm, and lead aVF is recorded from the left leg. In these leads, a stands for augmented; V stands for voltage; and R, L, and F indicate the location of the unipolar lead (right arm, left arm, and foot [left]). A normal ECG from these leads is illustrated in Fig. 17.31.
FIG 17.30 Unipolar augmented leads aVR, aVL, and aVF.
FIG 17.31 Normal electrocardiogram recorded from the three unipolar augmented leads. The aVR lead is characterized by a large S wave and an inverted T wave. The aVL and aVF leads have an upright R wave and T wave.
Precordial unipolar chest leads are recorded from electrodes placed in six positions over the heart on the anterior chest (Fig. 17.32). Chest leads are designated as V1, V2, V3, V4, V5, and V6. The normal ECG from the chest leads is shown in Fig. 17.33. The chest leads provide a horizontal view of the heart, whereas the limb leads provide a view of the frontal plane.
FIG 17.32 Unipolar chest (precordial) leads V1 through V6.
FIG 17.33 Normal electrocardiogram recorded from the six unipolar chest leads, V1 through V6. Note the progression across the precordial leads as the R waves become increasingly positive.
Twelve-lead ECGs are usually recorded for a short period when the patient is resting (Fig. 17.34). Sequential ECGs are useful for determining changes over time. In some cases it is necessary to monitor the ECG recording for an extended period to capture rhythm problems that occur infrequently or with particular activities. This is accomplished by continuous ambulatory monitoring (e.g., Holter monitoring) over a 24- to 48-hour period. An ECG can also be recorded during exercise to monitor the effects of exercise stress on cardiovascular function. An exercise test (stress test) is usually performed while the subject progressively increases his or her effort on a treadmill or stationary bicycle. The exercise ECG is particularly useful for assessing the adequacy of coronary circulation when the myocardial workload is increased. Impaired myocardial oxygen delivery may be evident on the ECG as ST segment elevation or depression and abnormal T waves.
FIG 17.34 Example of a normal 12-lead ECG showing R wave progression in V leads.
Magnetic Resonance Imaging and Computed Tomography
Magnetic resonance imaging (MRI) and computed tomography (CT) are useful for imaging cardiac structures. Myocardial thickening, pericardial sac disease, valvular structures, and congenital malformations may be visualized by MRI. Contrast-enhanced imaging identifies acute and chronic myocardial infarcts with high specificity and sensitivity. MRI and CT are used to detect coronary plaque burden and assess vulnerable plaque morphology in the arterial walls. Excessive plaque burden and unstable plaques are correlated with a greater degree of coronary atherosclerosis and may be used to predict coronary artery disease risk or progression.
Echocardiography
Echocardiography uses reflected sound waves (ultrasound) to provide an image of cardiac structure and motion within the chest. The cardiac echo is obtained by placing a blunt probe on the chest surface, which transmits and receives high-frequency sound waves. Sound waves traveling through chest and heart structures are reflected back to the receiving probe. The time between sound wave emission and detection of reflected waves is used to calculate distances between the probe and reflecting tissue. The sound waves are not heard or felt by the subject and have no known detrimental effects on tissues. The probe is moved across the chest to assess cardiac structures of interest, and recordings are videotaped for later viewing.
Echocardiograms are particularly useful for diagnosis of heart enlargement, valvular disorders, collections of fluid in the pericardial space, cardiac tumors, and abnormalities in left ventricular motion. Estimations of ejection fraction and assessments of ventricular systolic and diastolic function can be made noninvasively by echocardiogram. An echocardiogram is shown in Fig. 17.35.
FIG 17.35 Pathology specimen (left) and echocardiography image (right) of heart with enlarged right atrium and right ventricle. LA, Left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. (From Connolly H, Oh J: Echocardiography. In Bonow R et al, editors: Braunwald’s heart disease: a textbook of cardiovascular medicine, ed 9, vol 1, Philadelphia, 2012, Saunders, p 264.)
Nuclear Cardiography
Radioactive substances injected into the bloodstream can be used to trace the patterns of blood flow in the heart. Radiation exposure is minimal because very small amounts of radioactive substances are used. Radioactive tracers can be linked to substances that accumulate in normal myocardial cells while the tracer is delivered by coronary blood flow. Areas with impaired perfusion will absorb less radioactivity and appear as “cold spots” on the scan. Scanning usually is done using single-photon emission computed tomography (SPECT), which images numerous slices through the heart, or by planar imaging, which gives an overall picture in one plane only.
Thallium-201 (201Tl) and technetium-99 labeled compounds (99mTc sestamibi) are used to assess the adequacy of blood flow to cardiac tissues. After injection of the radioactive compound, the heart is scanned to visualize the amount of radioactivity absorbed by cardiac tissues. Healthy cardiac tissues that receive adequate blood supply actively accumulate these isotopes. Areas of inadequate blood flow or infarcted tissue do not accumulate isotopes and appear as cold spots on the scan. Resting and exercise scanning are done to assess for exercise-induced perfusion defects.
Gated pool scanning (radionuclide ventriculogram) is used primarily to assess left ventricular motion and ejection fraction. Before it is injected intravenously, radioactive technetium is attached to albumin or red blood cells, and therefore it remains in the bloodstream and is not absorbed by cells. Computer imaging is used to analyze blood flow through the chambers of the heart over many cardiac cycles. The dynamics of ventricular motion, such as hypercontractility or hypocontractility, may be visualized. Separate radionuclide ventriculogram evaluation has largely been replaced by SPECT scanning that allows simultaneous evaluation of perfusion and left ventricular function.
Positron emission tomography scans may also be used to evaluate cardiac perfusion and metabolism. Radiotracers can be incorporated into substances normally used in cellular metabolic processes, such as glucose. Metabolic activity in different areas of the heart can then be tracked over time under different conditions.
Cardiac Catheterization/Coronary Angiography
Cardiac catheterization/coronary angiography may be used to determine important structural and hemodynamic characteristics because it affords direct measurement of pressures within cardiac chambers; visualization of chamber size, shape, and movement; sampling for blood oxygen content in various heart regions; measurement of cardiac output and ejection fraction; and visualization and management of coronary artery obstructions.
Cardiac catheterization angiography is associated with several serious risks, including bleeding, dysrhythmias, heart perforation, and coronary ischemia. The advent of noninvasive high-resolution MRI, echocardiograms, and SPECT scanning has replaced the need for cardiac catheterization in many instances; however, the value of information supplied is generally believed to outweigh the risks in certain cases. Catheterization is frequently used for interventions to rapidly improve coronary blood supply and to evaluate suspected or confirmed coronary artery disease, valvular dysfunction, congenital defects, left ventricular dysfunction, and coronary bypass graft patency.
Assessment of the left side of the heart, including the coronary arteries, is achieved by passing a catheter through a femoral or brachial artery into the aorta. The catheter is then manipulated into the left ventricle or left atrium to assess chamber pressures, and a ventriculogram is obtained. Contrast dye injected into the ventricular chamber is monitored fluoroscopically to assess ventricular function. The catheter is usually pulled back into the aorta and then advanced into one or more of the coronary arteries. The patency of the coronary arteries can be visualized by injecting contrast dye into them and monitoring by fluoroscopy (Fig. 17.36). When contrast dye is in the coronary artery, a period of cardiac ischemia is produced during which the patient may experience angina, dysrhythmias, and coronary spasms. Coronary catheterization may also be done to insert a probe for obtaining intracoronary ultrasounds. Ultrasounds are useful for assessing plaque morphologic characteristics (Fig. 17.37).
FIG 17.36 Coronary artery angiography. The arrows show an area of obstruction of the coronary artery. (From Popma J et al: Coronary arteriography and intracoronary imaging. In Mann D et al, editors: Braunwald’s heart disease: a textbook of cardiovascular medicine, ed 10, Philadelphia, 2015, Saunders, p 414.)
FIG 17.37 Intracoronary ultrasonographic examples of plaque morphology. A, A normal vessel wall. B, Fibrous cap on coronary plaque. C, A soft plaque with rupture of the fibrous cap. (From Braunwald E, Zipes D, Libby P, editors: Braunwald’s heart disease: a textbook of cardiovascular medicine, ed 6, Philadelphia, 2001, Saunders, p 416.)
Right-sided heart catheterization is done to evaluate right-sided heart structures. The catheter is introduced into a vein, usually femoral, and then threaded through the inferior vena cava and into the heart. Pressures and blood samples are obtained as the catheter is advanced into the right atrium, ventricle, and pulmonary artery. Right heart catheterization is useful in assessing tricuspid and pulmonary valve disorders, pulmonary hypertension, septal defects, and right ventricular function.
Coronary angiography is commonly followed by interventions to treat detected abnormalities. The coronary catheter can be used to direct thrombolytic agents to the site of coronary thrombosis and rapidly restore blood flow to ischemic areas. Laser therapy, coronary balloon angioplasty, and stent placement can also be performed during coronary angiography. These methods clear the coronary obstruction through thermal and mechanical means. The success of these approaches to management of coronary obstruction depends largely on how soon after an ischemic event they are performed (see Chapter 18).
Summary
The heart’s primary function is to pump sufficient blood to deliver oxygen and nutrients to the body. The heart may be viewed as two separate pumps: a right-sided pump that perfuses the lungs and a left-sided pump that perfuses the systemic circulation. The left ventricle must generate higher pressures and therefore has a thicker myocardial mass and higher energy requirements. Because little ATP storage in cardiac cells is possible, the coronary arteries must deliver a steady supply of oxygen and nutrients. Cardiac contraction can be described by the sliding filament/cross-bridge theory and occurs only in the presence of ATP and free calcium ions. Factors that enhance intracellular calcium ion concentration will result in generation of a greater contractile force.
A coordinated cardiac contraction is possible because the heart’s conduction system activates the chambers in a sequential manner. The sinoatrial node is the usual pacemaker because it has the highest intrinsic rate of diastolic depolarization. The diastolic depolarization rate is strongly influenced by the autonomic nervous system. The ECG shows the electrical activity of the heart and is a useful indicator of cardiac conduction abnormalities.
The ultimate indicator of cardiac function is the cardiac output, which is the product of heart rate and stroke volume. The autonomic nervous system is the main regulator of heart rate, whereas stroke volume is influenced by preload, afterload, and contractility. These factors are also the primary determinants of myocardial work and energy expenditure.
Resources
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Fang JC, O’Gara PT. The history and physical examination: an evidence-based approach. Mann D, Zipes D, Libby P, Bonow R. Braunwald’s heart disease: a textbook of cardiovascular medicine. ed 10. Saunders: Philadelphia; 2015:95–113.
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