Pericardium. 

The heart and the origins of the great vessels are surrounded and enclosed by the pericardium. The outermost fibrous pericardium is a thick envelope that is tough and inelastic. Ligaments anchor the outer pericardium to the diaphragm and the great vessels such that the heart is maintained in a fixed position within the thoracic cavity. The pericardium also provides a physical barrier to infection. Inside the fibrous layer is an inner, double-walled membrane described as the serous pericardium.⁴ The two layers are labeled “parietal” and “visceral.” The parietal pericardium adheres to the tough, outer pericardium. The visceral pericardium is flexible, adheres directly to the heart, and folds with the surface contours of the heart. The pericardial cavity is the potential space between the visceral and parietal layers.^4,5 The space between these two layers normally contains a small amount of pericardial fluid, which is secreted, resorbed, and serves as a lubricant between the layers so that the heart can move without friction.⁵ The fibrous, outer pericardial sac is noncompliant and unable to adapt to rapid increases in pericardial fluid.⁵ For example, blood can collect in this sac in cardiac tamponade, or serum can collect in pericardial effusion. If the fluid collection in the sac impinges on ventricular filling, ventricular ejection, or coronary artery perfusion, removal of the excess pericardial fluid may be necessary, a procedure known as pericardiocentesis.⁵ The phrenic nerve provides sensory fibers to the pericardium. The pain that accompanies pericardial effusion and cardiac tamponade is sensed via phrenic nerve innervation.⁵

Epicardial Fat. 

In adults, a layer of adipose tissue is typically present beneath the visceral pericardium and may surround the heart. This epicardial fat accumulates along the routes of the major coronary arteries and veins. Autopsy data indicate that epicardial fat increases until age 20 to 40 years, but thereafter, the quantity does not depend on age.⁶ Epicardial fat covers 80% of the surface of the heart and constitutes about 20% of the total weight of the heart, with the largest quantity positioned over the right ventricle.⁶ If a person is overweight or obese with a large quantity of visceral and subcutaneous adipose tissue, usually more epicardial fat is present.⁷ Because obesity is endemic in modern society, epicardial fat is receiving more attention. Epicardial fat is hypothesized to increase the risk of coronary artery disease (CAD) because it contains smaller adipocytes compared with other fat deposits, has a different fatty acid composition, and has a higher protein content. This composition facilitates the infiltration of free fatty acids and adipokines into coronary arteries.⁸ The fibrous, outer pericardium does not contain any fat deposits.

Epicardium. 

The epicardium is tightly adhered to the heart and the base of the great vessels as described earlier. The coronary arteries lie on the top of the visceral epicardium.

Myocardium. 

The next layer of the heart is the myocardium, a thick, muscular layer. This layer includes all of the atrial and ventricular muscle fibers necessary for contraction. The fibers of the myocardium do not have the same thickness throughout the ventricular walls. The left ventricle is much thicker than the right ventricle or the atria. The fibers are organized in such a manner that the force of contraction is most efficient in ejecting blood toward the outflow tracts in a wringing motion from the apex toward the base (Fig. 12-2).⁹ The myocardium is the muscle that is damaged by a “heart attack” or transmural myocardial infarction (MI).

Endocardium. 

The innermost layer is the endocardium, which is a thin layer of endothelium and connective tissue lining the inside of the heart. This layer is continuous with the endothelium of the great vessels to provide a continuous closed system. Disruption in the endothelium as a result of surgery, trauma, or congenital abnormality can predispose the endocardium to infection. This infective endocarditis is a devastating disease, which, if left untreated, can lead to massive valve damage or sepsis and death.

Atrioventricular Valves. 

The two atrioventricular (AV) valves are named for their location between the atria and the ventricles. These are the tricuspid valve on the right and the mitral valve on the left. The mitral valve is described as having two leaflets, although the “leaflets” are a continuous, noninterrupted structure.¹¹ The AV valves are open during ventricular diastole (filling) and prevent backflow of blood into the atria during ventricular systole (contraction). The chordae tendineae and papillary muscles, which attach to the tricuspid and mitral valves, give the valves stability and prevent valve leaflet eversion during systole (Fig. 12-5). Papillary muscles arise from the ventricular myocardium and derive their blood supply from the coronary arteries. Each papillary muscle gives rise to approximately 4 to 10 main chordae tendineae, which divide into increasingly finer cords as they approach and attach to the valve leaflets. The chordae tendineae are fibrous, avascular structures covered by a thin layer of endocardium. Dysfunction of the chordae tendineae or of a papillary muscle may cause incomplete closure of an AV valve, which results in backflow of blood into the atrium. Degenerative disease of the valve leaflets is another cause of regurgitation of blood into the atrium.¹² Valvular regurgitation produces a murmur that can be auscultated with a stethoscope.

Semilunar Valves. 

The semilunar valves are pulmonic and aortic valves. Each valve has three cuplike leaflets (Fig. 12-6). These valves separate the ventricles from their respective outflow arteries (Table 12-1). During ventricular systole (contraction), semilunar valves open, allowing blood to flow out of the ventricles. As systole ends and the pressure in the outflow arteries exceeds that of the ventricles, the semilunar valves close, preventing blood regurgitation back into the ventricles. In most individuals, the aortic valve has three leaflets. In less than 1% of the population, it is bicuspid (a two-leaflet valve), which increases susceptibility to aortic valve failure over time.^13,14 Aortic valve dysfunction, from any cause, not only affects the valve leaflets but also pathologically alters the shape of the left ventricle.

Sinoatrial Node. 

The SA node is considered the natural pacemaker of the heart because it has the highest degree of automaticity, producing the fastest intrinsic heart rate (Table 12-2). The node is a spindle-shaped structure located near the entrance of the superior vena cava, on the posterior aspect of the right atrium. Some normal variability in the position and shape of the node exists. The SA node is supplied from the right coronary system in 63% of people and from the left coronary system in 37%.¹⁶ The SA node contains two types of cells, the specialized pacemaker cells found in the node center and the border zone cells. Both cell types have inherent pacemaker properties (they automatically depolarize 60 to 100 times per minute). The cells in the nodal center are responsible for the pace making of the heart, whereas the intrinsic depolarization capability of the fibers in the border zone is depressed by surrounding atrial tissue.

Once the center nodal cells depolarize, the impulse is conducted through the nodal border zone toward the atrium. Atrial depolarization occurs cell to cell. Some anatomists postulate that specialized conduction pathways exit the SA node (Fig. 12-7A). These internodal pathways are directed to the AV node.¹⁷ An intra-atrial conduction pathway, known as Bachmann’s bundle, travels from the right atrium to the left atrium.^18,19

Atrioventricular Node. 

The AV node is located posteriorly on the right side of the interatrial septum, on the floor of the right atrium.²⁰ The AV node receives its blood supply from the first posterior septal branch of the right (90%) or left (10%) coronary artery.¹⁶ Because the atria and ventricles are separated by nonconductive tissue, electrical impulses initiated in the atria are conducted to the ventricles only via the AV node. The AV node performs four essential functions to support cardiac conduction:

Bundle of His, Bundle Branches, and Purkinje Fibers. 

Electrical impulses are conducted in the ventricles through the bundle of His, the bundle branches, and the Purkinje fibers (see Fig. 12-7C). These structures run through the subendocardium, down the right side of the interventricular septum. About 12 mm from the AV node, the bundle of His divides into the right and left bundle branches. The right bundle branch continues down the right side of the interventricular septum toward the right apex. The left bundle branch is thicker than the right and takes off from the bundle of His at an almost right angle. It traverses the septum to the subendocardial surface of the left interventricular wall, where it divides into a thin anterior branch and a thick posterior branch. Functionally, when one of the left branches is blocked, it is referred to as a hemiblock. All of the bundle branches are subject to conduction defects (bundle branch blocks) that give rise to characteristic changes in the 12-lead electrocardiogram (ECG).

The right bundle branch and the two divisions of the left bundle branch eventually divide into the Purkinje fibers, which have the fastest conduction velocity of all heart tissue. Purkinje fibers divide many times, terminating in the subendocardial surface of both ventricles. This is followed by ventricular muscle depolarization (see Fig. 12-7D).

Coronary Veins. 

The cardiac (coronary) veins, which carry deoxygenated blood, are adjacent to the paths of the coronary arteries, with one significant difference. The coronary veins ultimately join together to become the coronary sinus (the largest cardiac vein), which primarily empties into the back of the right atrium. The coronary venous blood then mixes with the systemic venous blood in the right atrium.²²

Physiologic Cardiac Shunts. 

A shunt occurs when deoxygenated blood (usually venous blood with reduced oxygen content) mixes with arterial oxygenated blood. In the heart in a specific situation, this is a normal physiologic process. The thebesian veins are small vessels that connect the capillary beds directly with the cardiac chambers via irregular endothelium-lined sinuses within the myocardium. The thebesian veins add a small quantity of deoxygenated blood to the oxygenated blood in the left ventricle.

An example of an abnormal, or pathologic, intracardiac shunt is an opening in the ventricular septum, between the left and right sides of the heart. In the ventricle, this septal opening, called a ventricular septal defect (VSD), allows mixing of blood from both ventricles. The clinical impact depends on the size of the intracardiac shunt. A VSD is a congenital opening between the ventricles; a ventricular septal rupture (VSR) can occur as a complication of a large anterior-wall MI, as shown in Figure 15-15.

Arterial System. 

Arteries are constructed of three layers (Fig. 12-11): 1) The adventitia, the outermost layer, is composed largely of a connective tissue coat to provide strength and shape to the vessel; 2) the media, or muscular middle layer, is made up of smooth muscle and elastic tissue. The muscular layer changes the lumen diameter when necessary; and 3) the innermost layer, or intima, consists of a thin lining of endothelium and a small amount of elastic tissue. The smooth endothelial lining decreases resistance to blood flow and minimizes opportunity for platelet aggregation.

The intimal and the adventitial layers remain relatively constant in the vascular system, whereas the elastin and smooth muscle in the media vary in proportion, depending on the size and type of the vessel. The aorta contains the greatest amount of elastic tissue. This is necessary because of the sudden shifts in pressure created by the left ventricle. The arterioles, or smaller arteries, and precapillary sphincters have more smooth muscle than do the larger arteries and aorta because they function to change the luminal diameter when regulating blood pressure and blood flow to tissues (Fig. 12-12).

Blood Flow and Blood Pressure. 

The pulsatile nature of arterial flow is caused by intermittent cardiac ejection and the stretch of the ascending aorta. The pressure wave initiated by left ventricular ejection (Fig. 12-13) travels considerably faster than does blood itself. When an examiner palpates a pulse, it is the propagation of the pressure wave that is perceived.

In the normal arterial system, blood flow is described as laminar, or streamlined, because the fluid moves in one direction. However, differences exist in the linear velocities within a blood vessel. The layer of blood immediately adjacent to the vessel wall moves relatively slowly because of the friction created as it comes in contact with the motionless vessel wall. In contrast, the more central blood in the lumen travels more rapidly (Fig. 12-14).

Clinical implications include conditions in which the vessel wall has an abnormality such as a small clot or plaque deposit. This disruption in the streamlined flow can set up eddy currents that may predispose the area to platelet aggregation and atherosclerosis.

Blood pressure measurement has several components. The systolic blood pressure (SBP) represents the ventricular volume ejection and the response of the arterial system to that ejection. The diastolic blood pressure (DBP) value indicates the ventricular resting state of the arterial system. The pulse pressure is the difference between the SBP and the DBP. The mean arterial pressure (MAP) is the mean value of the area under the blood pressure curve (Fig. 12-15). Blood pressure may be measured in several ways. Direct measurement is accomplished by means of a catheter inserted into an artery. Blood pressure is measured in millimeters of mercury (mm Hg). The most common indirect method is by means of a stethoscope and sphygmomanometer (Fig. 12-16). Figure 12-17 graphically summarizes blood pressures in various portions of the systemic circulatory system.

Vascular resistance is a reflection of arteriolar tone. The large amount of smooth muscle in the arterioles allows for relaxation or contraction of these vessels, which causes changes in the resistance and redistribution of blood flow. Resistance is the opposition to flow caused by the blood vessels. Most changes in resistance are caused by alterations in the tone of the arterial vessel walls, especially in the arterioles. The purpose of this mechanism is to maintain a constant blood pressure in the arterial system. The clinician can never assume that blood flow and blood pressure are identical. For example, poor blood flow to the tissues because of vasoconstricted peripheral arterioles causes the blood to back up and increases the blood pressure. A higher blood pressure is a compensatory mechanism but does not necessarily mean that tissue perfusion is adequate.

It is also possible to calculate the resistance within the systemic vascular system, described by the phrase systemic vascular resistance (SVR). When it occurs in the pulmonary circulation, it is termed pulmonary vascular resistance (PVR). These derived values are based on calculations from other hemodynamic parameters, as described in Chapter 14 and Appendix B.

Microcirculation. 

The microcirculation consists of arterioles, arterial capillaries, venous capillaries, and venules (Fig. 12-18). Oxygen, nutrients, hormones, and waste products are exchanged between the bloodstream and adjacent cells. The microcirculation has a vital role in the regulation of oxygen supply and demand at the tissue level. The density and anatomy of the microcirculation vary, depending on the metabolic needs of each tissue or organ.

Precapillary sphincters are small cuffs of smooth muscle that control blood flow at the junction of the arterioles and the capillaries. The precapillary sphincters allow selective blood flow into capillary beds, depending on their contractile state, and are innervated by norepinephrine released from the sympathetic nervous system (SNS) and epinephrine released by chromaffin cells in the adrenal medulla of the adrenal glands.²³

As blood reaches the capillary level, the pulsatile nature of arterial flow is dampened (see Fig. 12-17). Even though the diameter of a capillary is less than that of an arteriole, the pressure and flow velocity in the capillary bed is low as a result of the large cross-sectional area of the branching capillary bed (see Fig. 12-18). The capillary consists of a single cell layer of endothelium and is devoid of muscle or elastin (see Fig. 12-12). This arrangement allows solutes to diffuse in and out of the capillaries unimpeded by mechanical barriers. The capillaries normally retain large structures such as red blood cells but are highly permeable to smaller solutes such as electrolytes.

Phase 0. 

The sodium crossing the cell membrane causes the cell to become depolarized and the interior of the cell to become more positive. At approximately −65 mV, the membrane reaches the threshold, the point at which the inward Na⁺ current overcomes the efflux of K⁺. This is accomplished by means of the fast Na⁺ channels. With the fast Na⁺ channels open, the inward rush of Na⁺ is extremely rapid and briefly causes the inside of the cell to become slightly more positive than the outside of the cell. This series of events is graphically described as phase 0 of the AP and is reflected in the overshoot of the AP, during which the charge is 20 to 30 mV.

Phase 1 and Phase 2. 

When the rapid influx of Na⁺ is terminated, a brief period of partial repolarization occurs as the AP slope returns toward zero (phase 1 of the AP). The plateau that follows is described as phase 2. During this phase, another set of channels, the slow Na⁺ and Ca²⁺ channels, open to allow the influx of Ca²⁺ and Na⁺. During phase 2, K⁺ tends to diffuse out of the cell, balancing the slow inward flux of Na⁺ and Ca²⁺ thereby maintaining the plateau of the AP. The Ca²⁺ entering the cell at this phase causes cardiac contraction, which is described later in this chapter. The inward flux of Ca²⁺ during this phase can be influenced by many factors. For example, calcium channel–blocking medications such as verapamil and diltiazem inhibit the inward Ca²⁺ current into pacemaker tissue, especially the AV node. For this reason, this class of medications is used therapeutically to slow the rate of atrial tachydysrhythmias and protect the ventricle from excessive atrial impulses, as described in the section on cardiac medications in Chapter 16.

Phase 3. 

The repolarization phase is described as phase 3, and it depends on two processes. The first is the inactivation of the slow channels, which prevents further influx of Ca²⁺ and Na⁺. The other is the continued efflux of K⁺ out of the cell. Both processes cause the intracellular environment to become more negative, thereby re-establishing the RMP. On the AP, phase 3 is seen as a gradual descent during which the interior of the cell becomes more negative relative to the outside.

Phase 4. 

In phase 4, the AP returns to an RMP of −80 to −90 mV. The excess Na⁺ that entered the cell during depolarization is removed from the cell in exchange for K⁺ by means of the Na⁺–K⁺ pump. This mechanism returns the intracellular concentrations of Na⁺ and K⁺ to the levels present before depolarization and is essential for normal ionic balance and preparation for the next depolarization (see Table 12-5).

Fiber Conduction and Excitability. 

Different parts of the conduction system require different electrical currents and create individual transmembrane APs, as shown in Figure 12-7 earlier in the chapter. Ionic shifts within the endocardium, myocardium, and epicardium are not uniform, although the clinical significance of this finding is not clear. Propagation of an AP along a cardiac fiber occurs as a result of ionic shifts (discussed earlier). As a local section of the cell becomes depolarized, reaches threshold, and completely depolarizes, it affects the adjacent area of the cell and initiates depolarization in that area. The AP propagates down the fiber in a wavelike fashion (Fig. 12-24). This is somewhat analogous to a trail of gunpowder. When the gunpowder is lit at one end, a small area ignites, burns, and then ignites the area of gunpowder immediately adjacent to it and on down the line.

The time from the beginning of the AP until the fiber can accept another AP is called the effective or absolute refractory period. During this period, the cell cannot be depolarized regardless of the amount or intensity of the stimulus. This period lasts from the beginning of depolarization until the interior of the cell has repolarized to approximately −50 mV during phase 3. The absolute refractory period is immediately followed by the relative refractory period. At this time, the cell is not fully repolarized but could depolarize with a strong enough stimulus (Fig. 12-25). This period lasts from approximately −50 mV during phase 3 until the cell returns to RMP (phase 4); at that point, the cell is fully repolarized and is again ready to respond to the next stimulus. The concept of relative versus absolute refractory periods is useful for understanding the genesis of ventricular dysrhythmias (see Chapter 14). In brief, a cell cannot be stimulated to depolarize until it has at least partially recovered from the previous impulse. This means that an ectopic impulse cannot be propagated during the absolute refractory period.

Pacemaker Cell versus Non-pacemaker Cell Action Potentials. 

The AP is representative of the depolarization of non-pacemaker myocardial cells. The AP generated by a Purkinje fiber is similar to that of a ventricular myocardial cell except that phase 2 is usually more prolonged in the Purkinje fiber. Atrial myocardial cells exhibit a shortened plateau (phase 2) compared with ventricular cells. The pacemaker cells of the SA node have an AP that is very different from that of a myocardial cell or a Purkinje cell. In the SA node, the RMP is not as negative, approximately −65 mV. Rather than having an RMP that remains constant, the pacemaker cells slowly depolarize at a steady rate until the threshold is reached (see Fig. 12-23B). The lack of a steady-state RMP is largely the result of a continual Na⁺ influx through the slow channels. This mechanism explains how the cells can spontaneously depolarize (automaticity). It also provides the basis for understanding alterations in the pacemaker cells. The frequency of pacemaker cell discharge may be altered by changing the rate of depolarization or by raising or lowering the cellular RMP.

Baroreceptors. 

Baroreceptors, or pressure sensors, are located in the aortic arch and the carotid sinuses.²⁹ They are more sensitive to wall changes (wall stretch) in these areas than to the absolute pressure. As the receptors sense a change in wall conformation, usually as a result of a change in pressure, the ANS is activated to raise HR (in the case of decreased pressure) or lower it (in response to increased pressure). For example, a decrease in blood pressure alters the baroreceptor input to the vasomotor center in the medulla (brainstem), causing a reflex tachycardia. The baroreflex also initiates changes in venous tone to alter CO according to need. Venoconstriction increases blood return to the heart and augments SV.

Chemoreceptors. 

The arterial chemoreceptors, or carotid and aortic bodies, are located in the carotid arteries and at the bifurcation of the aortic arch.³⁰ They possess a rich capillary blood supply and extensive innervation of the PNS. Their primary function is to maintain homeostasis during hypoxemia.³⁰ Chemoreceptors signal changes in oxygen tension (Pao₂ <80 mm Hg), or a carbon dioxide tension (Paco₂) of greater than 40 mm Hg, but not to changes in acid–base balance (pH). Changes in the pH level are detected by the central chemoreceptors in the brainstem (medulla oblongata). Information about changes in these parameters is communicated to the SNS via the brainstem altering HR. Stimulation of the carotid or aortic chemoreceptors normally causes an increase in respiratory rate and depth.

Right Atrial Receptors. 

The Bainbridge reflex is attributed to receptors in the right and left atria.³¹ When the pressure in the right atrium rises sufficiently to stimulate the stretch receptors, it causes a reflex tachycardia. The purpose of this reflex is possibly to protect the right side of the heart from an overload state and to quickly equalize filling pressures of the right and left sides of the heart.

Natriuretic Peptides. 

Another cardiac control mechanism involves the natriuretic peptide system (Fig. 12-30). The heart secretes two major natriuretic peptides. The atrial myocardium secretes atrial natriuretic peptide (ANP) in response to atrial stretch, and the ventricular myocardium secretes brain natriuretic peptide (BNP) if stretch of the ventricular chamber occurs. Both peptides cause vasodilatation, increase natriuresis (Na⁺ and water loss via the kidneys), and inhibit the SNS and the renin–angiotensin–aldosterone system (RAAS).³² Clinically, BNP levels are measured to confirm the diagnosis of acute heart failure. A recombinant form of human BNP, nesiritide (Natrecor), is used therapeutically to mimic the clinical effects of BNP and treat symptoms of heart failure.

Renin–Angiotensin–Aldosterone System. 

The RAAS system is activated by low blood pressure or intravascular volume depletion. The juxtaglomerular cells of the kidney, located near the afferent arteriole, are activated by low renal blood flow. As shown in Table 12-7, this stimulates release of the hormone renin. Renin converts the protein angiotensinogen to angiotensin I. When angiotensin I passes through the pulmonary vascular bed, it is activated by angiotensin-converting enzyme (ACE) to become angiotensin II. Angiotensin II is a powerful agent with two principal actions: 1) It activates peripheral vascular receptors to vasoconstrict the systemic arterial system and increase blood pressure, and 2) it activates the release of aldosterone from the adrenal glands. Aldosterone works at the distal convoluted tubule in the kidney to retain sodium and, consequently, water. Many medications are used to manipulate the RAAS system to manage symptoms of heart failure (see “Heart Failure” in Chapter 15 and “Cardiac Medications” in Chapter 16).

Respiratory Influences. 

Other influences involve the respiratory cycle and its effect on HR and SV. Normally, HR varies slightly with the respiratory cycle. The heart usually accelerates on inspiration and decelerates with exhalation (see “Sinus Dysrhythmia” in Chapter 14). Left ventricular SV decreases during normal inspiration. Possible reasons include normal fluctuations in sympathetic and vagal tones during respiration or any of the following alterations: decreased intrathoracic pressure contributing to increased venous return; the Bainbridge reflex; activation of stretch receptors in the lungs; interactions between the respiratory and cardiac centers in the medulla; increased capacity of the pulmonary vessels during lung inflation; decreased left ventricular compliance resulting from increased right ventricular return; increased impedance to left ventricular outflow related to the pleural pressure changes; or neural reflex mechanisms that are independent of mechanical influences.