The systemic vasculature can be divided functionally into arteries, arterioles, capillaries, and veins. Arteries are the high-pressure conduits that supply the various organs. Arterioles are the small vessels that directly feed and control blood flow through each capillary bed. Capillaries are thin-walled vessels that allow the exchange of nutrients between blood and tissues. Veins return blood from capillary beds to the heart.
The distribution of blood between the various components of the circulatory system is shown in Table 20–6. Note that most of the blood volume is in the systemic circulation—specifically, within systemic veins. Changes in systemic venous tone allow these vessels to function as a reservoir for blood. Following significant blood or fluid losses, a sympathetically mediated increase in vascular tone reduces the capacity of these vessels and shifts blood into other parts of the vascular system. Conversely, increased capacity (“venodilation”) allows these vessels to accommodate increases in blood volume. Sympathetic control of vascular tone is an important determinant of venous return to the heart. Reduced venous tone following induction of anesthesia frequently results in pooling of blood, reduced cardiac output, and hypotension.
TABLE 20–6Distribution of blood volume. ||Download (.pdf) TABLE 20–6 Distribution of blood volume.
|Heart ||7% |
|Pulmonary circulation ||9% |
Many factors influence blood flow in the vascular tree, including metabolic products, endothelium-derived factors, the autonomic nervous system, and circulating hormones.
Most tissue beds regulate their own blood flow (autoregulation). Arterioles generally dilate in response to reduced perfusion pressure or increased tissue demand. Conversely, arterioles constrict in response to increased pressure or reduced tissue demand. These phenomena are likely due to both an intrinsic response of vascular smooth muscle to stretch and the accumulation of vasodilatory metabolic byproducts. The latter may include K+, H+, CO2, adenosine, and lactate.
The vascular endothelium is metabolically active in elaborating or modifying substances that directly or indirectly play a major role in controlling blood pressure and flow. These include vasodilators (eg, nitric oxide, prostacyclin [PGI2]), vasoconstrictors (eg, endothelins, thromboxane A2), anticoagulants (eg, thrombomodulin, protein C), fibrinolytics (eg, tissue plasminogen activator), and factors that inhibit platelet aggregation (eg, nitric oxide and PGI2). Nitric oxide is synthesized from arginine by nitric oxide synthetase. This substance has a number of functions. It binds guanylate cyclase, increasing cGMP levels and potently produces vasodilation. Endothelially derived vasoconstrictors (endothelins) are released in response to thrombin and epinephrine.
AUTONOMIC CONTROL OF THE SYSTEMIC VASCULATURE
Although the parasympathetic system can exert important influences on the circulation, autonomic control of the vasculature is primarily sympathetic. Sympathetic outflow to the circulation passes out of the spinal cord at all thoracic segments and the first two lumbar segments. These fibers reach blood vessels via specific autonomic nerves or by traveling along spinal nerves. Sympathetic fibers innervate all parts of the vasculature except for capillaries. Their principal function is to regulate vascular tone. Variations of arterial vascular tone serve to regulate blood pressure and the distribution of blood flow to the various organs, whereas variations in venous tone alter vascular capacity, venous pooling, and venous return to the heart.
The vasculature has sympathetic vasoconstrictor and vasodilator fibers, but the former are more important physiologically in most tissue beds. Sympathetic-induced vasoconstriction (via α1-adrenergic receptors) can be potent in skeletal muscle, kidneys, gut, and skin; it is least active in the brain and heart. The most important vasodilatory fibers are those feeding skeletal muscle, mediating increased blood flow (via β2-adrenergic receptors) in response to exercise. Vasodepressor (vasovagal) syncope, which can occur following intense emotional strain associated with high sympathetic tone, results from reflex activation of both vagal and sympathetic vasodilator fibers.
Vascular tone and autonomic influences on the heart are controlled by vasomotor centers in the reticular formation of the medulla and lower pons. Distinct vasoconstrictor and vasodilator areas have been identified. Vasoconstriction is mediated by the anterolateral areas of the lower pons and upper medulla. They are also responsible for adrenal secretion of catecholamines, as well as the enhancement of cardiac automaticity and contractility. Vasodilatory areas, which are located in the lower medulla, are also adrenergic. They function by projecting inhibitory fibers upward to the vasoconstrictor areas. Vasomotor output is modified by inputs from throughout the central nervous system, including the hypothalamus, cerebral cortex, and the other areas in the brainstem. Areas in the posterolateral medulla receive input from both the vagal and the glossopharyngeal nerves and play an important role in mediating a variety of circulatory reflexes. The sympathetic system normally maintains some tonic vasoconstriction on the vascular tree. Loss of this tone following induction of anesthesia or sympathectomy frequently contributes to perioperative hypotension.
Systemic blood flow is pulsatile in large arteries because of the heart’s cyclic activity; when the blood reaches the systemic capillaries, flow is continuous (laminar). The mean pressure falls to less than 20 mm Hg in the large systemic veins that return blood to the heart. The largest pressure drop, nearly 50%, is across the arterioles, and the arterioles account for the majority of SVR.
MAP is proportionate to the product of SVR × CO. This relationship is based on an analogy to Ohm’s law, as applied to the circulation:
Because CVP is normally very small compared with MAP, the former can usually be ignored. From this relationship, it is readily apparent that hypotension is the result of a decrease in SVR, CO, or both: To maintain arterial blood pressure, a decrease in either SVR or CO must be compensated by an increase in the other. MAP may be estimated by the following formula:
where pulse pressure is the difference between systolic and diastolic blood pressure. Arterial pulse pressure is directly related to stroke volume, but is inversely related to the compliance of the arterial tree. Thus, decreases in pulse pressure may be due to a decrease in stroke volume, an increase in SVR, or both. Increased pulse pressure increases shear stress on vessel walls, potentially leading to atherosclerotic plaque rupture and thrombosis or rupture of aneurysms. Increased pulse pressure in patients undergoing cardiac surgery has been associated with adverse renal and neurological outcomes.
Transmission of the arterial pressure wave from large arteries to smaller vessels in the periphery is faster than the actual movement of blood; the pressure wave velocity is 15 times the velocity of blood in the aorta. Moreover, reflections of the propagating waves off arterial walls widen pulse pressure before the pulse wave is completely dampened in very small arteries. Thus, the pulse pressure is generally greater when measured in the femoral or dorsalis pedis arteries than in the aorta.
Control of Arterial Blood Pressure
Arterial blood pressure is regulated by a series of immediate, intermediate, and long-term adjustments that involve complex neural, humoral, and renal mechanisms.
Minute-to-minute control of blood pressure is primarily the function of autonomic nervous system reflexes. Changes in blood pressure are sensed both centrally (in hypothalamic and brainstem areas) and peripherally by specialized sensors (baroreceptors). Decreases in arterial blood pressure result in increased sympathetic tone, increased adrenal secretion of epinephrine, and reduced vagal activity. The resulting systemic vasoconstriction, increased heart rate, and enhanced cardiac contractility serve to increase blood pressure.
Peripheral baroreceptors are located at the bifurcation of the common carotid arteries and the aortic arch. Elevations in blood pressure increase baroreceptor discharge, inhibiting systemic vasoconstriction and enhancing vagal tone (baroreceptor reflex). Reductions in blood pressure decrease baroreceptor discharge, allowing vasoconstriction and reduction of vagal tone. Carotid baroreceptors send afferent signals to circulatory brainstem centers via Hering’s nerve (a branch of the glossopharyngeal nerve), whereas aortic baroreceptor afferent signals travel along the vagus nerve. Of the two peripheral sensors, the carotid baroreceptor is physiologically more important and serves to minimize changes in blood pressure caused by acute events, such as a change in posture. Carotid baroreceptors sense MAP most effectively between pressures of 80 and 160 mm Hg. Adaptation to acute changes in blood pressure occurs over the course of 1 to 2 days, rendering this reflex ineffective for longer term blood pressure control. All volatile anesthetics depress the normal baroreceptor response, but isoflurane and desflurane seem to have less effect. Cardiopulmonary stretch receptors located in the atria, left ventricle, and pulmonary circulation can cause a similar effect.
In the course of a few minutes, sustained decreases in arterial pressure, together with enhanced sympathetic outflow, activate the renin–angiotensin–aldosterone system, increase secretion of arginine vasopressin (AVP), and alter normal capillary fluid exchange. Both angiotensin II and AVP are potent arteriolar vasoconstrictors. Their immediate action is to increase SVR. In contrast to formation of angiotensin II, which responds to relatively smaller changes, sufficient AVP secretion to produce vasoconstriction will only occur in response to more marked degrees of hypotension. Angiotensin constricts arterioles via AT1 receptors. AVP mediates vasoconstriction via V1 receptors and exerts its antidiuretic effect via V2 receptors.
Sustained changes in arterial blood pressure can also alter fluid exchange in tissues by their secondary effects on capillary pressures. Hypertension increases interstitial movement of intravascular fluid, whereas hypotension increases reabsorption of interstitial fluid. Such compensatory changes in intravascular volume can reduce fluctuations in blood pressure, particularly in the absence of adequate renal function (see below).
The effects of slower renal mechanisms become apparent within hours of sustained changes in arterial pressure. As a result, the kidneys alter total body sodium and water balance to restore blood pressure to normal. Hypotension results in sodium (and water) retention, whereas hypertension generally increases sodium excretion in normal individuals.
ANATOMY & PHYSIOLOGY OF THE CORONARY CIRCULATION
Myocardial blood supply is derived entirely from the right and left coronary arteries (Figure 20–15). Blood flows from epicardial to endocardial vessels. After perfusing the myocardium, blood returns to the right atrium via the coronary sinus and the anterior cardiac veins. A small amount of blood returns directly into the chambers of the heart by way of the thebesian veins.
Anatomy of the coronary arteries in a patient with a right dominant circulation. A: Right anterior oblique view. B: Left anterior oblique view.
The right coronary artery (RCA) normally supplies the right atrium, most of the right ventricle, and a variable portion of the left ventricle (inferior wall). In 85% of persons, the RCA gives rise to the posterior descending artery (PDA), which supplies the superior–posterior interventricular septum and inferior wall—a right dominant circulation; in the remaining 15% of persons, the PDA is a branch of the left coronary artery—a left dominant circulation.
The left coronary artery normally supplies the left atrium and most of the interventricular septum and left ventricle (septal, anterior, and lateral walls). After a short course, the left main coronary artery bifurcates into the left anterior descending artery (LAD) and the circumflex artery (CX); the LAD supplies the septum and anterior wall and the CX supplies the lateral wall. In a left dominant circulation, the CX wraps around the AV groove and continues down as the PDA to also supply most of the posterior septum and inferior wall.
The arterial supply to the SA node may be derived from either the RCA (60% of individuals) or the LAD (the remaining 40%). The AV node is usually supplied by the RCA (85–90%) or, less frequently, by the CX (10–15%); the bundle of His has a dual blood supply derived from the PDA and LAD. The anterior papillary muscle of the mitral valve also has a dual blood supply that is fed by diagonal branches of the LAD and marginal branches of the CX. In contrast, the posterior papillary of the mitral valve is usually supplied only by the PDA and is therefore much more vulnerable to ischemic dysfunction.
2. Determinants of Coronary Perfusion
Coronary perfusion is unique in that it is intermittent rather than continuous, as it is in other organs. During contraction, intramyocardial pressures in the left ventricle approach systemic arterial pressure. The force of left ventricular contraction almost completely occludes the intramyocardial part of the coronary arteries. Coronary perfusion pressure is usually determined by the difference between aortic pressure and ventricular pressure. The left ventricle is perfused almost entirely during diastole. In contrast, the right ventricle is perfused during both systole and diastole (Figure 20–16). Moreover, as a determinant of left heart myocardial blood flow, arterial diastolic pressure is more important than MAP. Therefore, left coronary artery perfusion pressure is determined by the difference between arterial diastolic pressure and left ventricular end-diastolic pressure (LVEDP).
Coronary blood flow during the cardiac cycle. (Modified with permission from Berne RM, Levy MD, Pappao A, et al. Cardiovascular Physiology. 10th ed. Philadelphia, PA Mosby; 2013.)
Decreases in aortic pressure or increases in ventricular end-diastolic pressure can reduce coronary perfusion pressure. Increases in heart rate also decrease coronary perfusion because of the disproportionately greater reduction in diastolic time as heart rate increases (Figure 20–17). Because the endocardium is subjected to the greatest intramural pressures during systole, it tends to be most vulnerable to ischemia during decreases in coronary perfusion pressure.
The relationship between diastolic time and heart rate.
Control of Coronary Blood Flow
Coronary blood flow normally parallels myocardial metabolic demand. In the average adult man, coronary blood flow is approximately 250 mL/min at rest. The myocardium regulates its own blood flow closely between perfusion pressures of 50 and 120 mm Hg. Beyond this range, blood flow becomes increasingly pressure dependent.
Under normal conditions, changes in blood flow are entirely due to variations in coronary arterial tone (resistance) in response to metabolic demand. Hypoxia—either directly, or indirectly through the release of adenosine—causes coronary vasodilation. Autonomic influences are generally weak. Both α1- and β2-adrenergic receptors are present in the coronary arteries. The α1-receptors are primarily located on larger epicardial vessels, whereas the β2-receptors are mainly found on the smaller intramuscular and subendocardial vessels. Sympathetic stimulation generally increases myocardial blood flow because of an increase in metabolic demand and a predominance of β2-receptor activation. Parasympathetic effects on the coronary vasculature are generally minor and weakly vasodilatory.
3. Myocardial Oxygen Balance
Myocardial oxygen demand is usually the most important determinant of myocardial blood flow. Relative contributions to oxygen requirements include basal requirements (20%), electrical activity (1%), volume work (15%), and pressure work (64%). The myocardium usually extracts 65% of the oxygen in arterial blood, compared with 25% in most other tissues. Coronary sinus oxygen saturation is usually 30%. Therefore, the myocardium (unlike other tissues) cannot compensate for reductions in blood flow by extracting more oxygen from hemoglobin. Any increases in myocardial metabolic demand must be met by an increase in coronary blood flow. Table 20–7 lists the most important factors in myocardial oxygen demand and supply. Note that the heart rate and, to a lesser extent, ventricular end-diastolic pressure are important determinants of both supply and demand.
TABLE 20–7Factors affecting myocardial oxygen supply–demand balance.
EFFECTS OF ANESTHETIC AGENTS
Most volatile anesthetic agents are coronary vasodilators. Their effect on coronary blood flow is variable because of their direct vasodilating properties, reduction of myocardial metabolic requirements, and effects on arterial blood pressure.
Volatile agents exert beneficial effects in experimental myocardial ischemia and infarction. They reduce myocardial oxygen requirements and protect against reperfusion injury; these effects are mediated by activation of ATP-sensitive K+ (KATP) channels. Some evidence also suggests that volatile anesthetics enhance recovery of the “stunned” myocardium (hypocontractile, but recoverable, myocardium after ischemia). Moreover, although volatile anesthetics decrease myocardial contractility, they can be potentially beneficial in patients with heart failure because most of them decrease preload and afterload.
The Pathophysiology of Heart Failure
Systolic heart failure occurs when the heart is unable to pump a sufficient amount of blood to meet the body’s metabolic requirements. Clinical manifestations usually reflect the effects of the low cardiac output on tissues (eg, fatigue, dyspnea, oxygen debt, acidosis), the damming-up of blood behind the failing ventricle (dependent edema or pulmonary venous congestion), or both. The left ventricle is most commonly the primary cause, often with secondary involvement of the right ventricle. Isolated right ventricular failure can occur in the setting of advanced disease of the lung parenchyma or pulmonary vasculature. Left ventricular failure is most commonly the result of myocardial dysfunction, usually from coronary artery disease, but may also be the result of viral disease, toxins, untreated hypertension, valvular dysfunction, arrhythmias, or pericardial disease.
Diastolic dysfunction can be present in the absence of signs or symptoms of heart failure, as for example in patients with hypertension or aortic valve stenosis. Symptoms arising from diastolic dysfunction are the result of atrial hypertension and pulmonary congestion (Figure 20–18). Failure of the heart to relax during diastole leads to elevated left ventricular end-diastolic pressure, which is transmitted to the left atrium and pulmonary vasculature. Common causes of diastolic dysfunction include hypertension, coronary artery disease, hypertrophic cardiomyopathy, valvular heart disease, and pericardial disease. Diastolic dysfunction is not the same as diastolic heart failure. In the patient with systolic heart failure the heart compensates by dilating, which leads to an increase in end-diastolic ventricular volume in an attempt to preserve the stroke volume. In patients with diastolic failure, poor ventricular relaxation leads to a higher LVEDP than would be noted in a patient without diastolic dysfunction for the same end-diastolic volume.
Ventricular pressure–volume relationships in isolated systolic and diastolic dysfunction.
Diastolic dysfunction is diagnosed echocardiographically. Placing the pulse wave Doppler sample gate at the tips of the mitral valve during left ventricular filling will produce the characteristic diastolic flow pattern (Figure 20–13). In patients with normal diastolic function, the ratio between the peak velocities of the early (E) and the atrial (A) waves is from 0.8 to 2. In the early stages of diastolic dysfunction, the primary abnormality is impaired relaxation. When left ventricular relaxation is delayed, the initial pressure gradient between the left atrium and the left ventricle is reduced, resulting in a decline in early filling, and, consequently, a reduced peak E wave velocity. The A wave velocity is increased relative to the E wave, and the E/A ratio is reduced. As diastolic dysfunction advances, the left atrial pressure increases, restoring the gradient between the left atrium and left ventricle with an apparent restoration of the normal E/A ratio. This pattern is characterized as “pseudonormalized.” Using the E/A ratio alone cannot distinguish between a normal and pseudonormalized pattern of diastolic inflow. As diastolic dysfunction worsens further, a restrictive pattern is obtained. In this scenario, the left ventricle is so stiff that pressure builds in the left atrium, resulting in a dramatic peak of early filling and a prominent, tall, narrow E wave. Because the ventricle is so poorly compliant, the atrial contraction contributes little to filling, resulting in a diminished A wave and an E/A ratio greater than 2:1.
Doppler patterns of pulmonary venous flow have been used to distinguish between a pseudonormalized and normal E/A ratio. Currently, most echocardiographers use tissue Doppler to examine the movement of the lateral annulus of the mitral valve during ventricular filling (Figure 20–13). Tissue Doppler allows the echocardiographer to determine both the velocity and the direction of the movement of the heart. During systole, the heart contracts toward the apex, away from a TEE transducer in the esophagus. This motion produces the s' wave of systole. During early and late diastolic filling, the heart moves toward the transducer producing the e' and a' waves. Like the inflow patterns achieved with pulse wave Doppler, characteristic patterns of diastolic dysfunction are reflected in the tissue Doppler trace. An e' wave less than 8 cm/s is consistent with diastolic dysfunction. Of note, the tissue Doppler trace does not produce a pseudonormalized pattern, permitting the echocardiographer to readily distinguish between normal and abnormal diastolic function.
Cardiac output may be reduced at rest with heart failure, but the key point is that the heart is incapable of appropriately increasing cardiac output and oxygen delivery in response to demand. Inadequate oxygen delivery to tissues is reflected by a low mixed venous oxygen tension and an increase in the arteriovenous oxygen content difference. In compensated heart failure, the arteriovenous difference may be normal at rest, but it rapidly widens during stress or exercise.
Compensatory mechanisms generally present in patients with heart failure include activation of the sympathetic nervous system and the renin–angiotensin–aldosterone system and increased release of AVP. One result is increased preload (fluid retention). Although these mechanisms can initially compensate for mild to moderate cardiac dysfunction, with increasing severity of dysfunction, they may actually worsen the cardiac impairment. Many of the drug treatments of chronic heart failure serve to counteract these mechanisms.
An increase in ventricular size not only reflects an inability to keep up with an increased circulating blood volume, but also serves to increase stroke volume by moving the heart up the Starling curve (see Figure 20–5). Even when EF is reduced, an increase in ventricular end-diastolic volume can maintain a normal stroke volume. Worsening venous congestion caused by the pooling of blood behind the failing ventricle and excessive ventricular dilation can rapidly lead to clinical deterioration. Left ventricular failure results in pulmonary vascular congestion and progressive transudation of fluid, first into the pulmonary interstitium and then into alveoli (pulmonary edema). Right ventricular failure leads to systemic venous hypertension, which results in peripheral edema, hepatic congestion and dysfunction, and ascites. Dilation of the annulus of either the mitral or tricuspid valves from ventricular dilation leads to valvular regurgitation, further impairing ventricular output.
Increased Sympathetic Tone
Sympathetic activation increases release of norepinephrine from nerve endings in the heart and secretion of epinephrine from the adrenal glands into the circulation. Although enhanced sympathetic outflow can initially maintain cardiac output by increasing heart rate and contractility, worsening ventricular function elicits increasing degrees of vasoconstriction in an effort to maintain arterial blood pressure. The associated increase in afterload, however, reduces cardiac output and exacerbates the ventricular failure.
Chronic sympathetic activation in patients with heart failure eventually decreases the response of adrenergic receptors to catecholamines (receptor uncoupling), the number of receptors (downregulation), and cardiac catecholamine stores. Nonetheless, the failing heart becomes increasingly dependent on circulating catecholamines. Abrupt withdrawal in sympathetic outflow or decreases in circulating catecholamine levels, such as can occur following induction of anesthesia, may lead to acute cardiac decompensation. A reduced density of M2 receptors also decreases parasympathetic influences on the heart.
Sympathetic activation tends to redistribute systemic blood flow output away from the skin, gut, kidneys, and skeletal muscle to the heart and brain. Decreased renal perfusion, together with β1-adrenergic activity at the juxtaglomerular apparatus, activates the renin–angiotensin–aldosterone axis, which leads to sodium retention and interstitial edema. Moreover, vasoconstriction secondary to elevated angiotensin II levels increases left ventricular afterload and causes further deterioration of systolic function. The latter partially accounts for the efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers in heart failure. Symptoms may also improve in some patients with careful, low-dose β-adrenergic blockade. Outcomes in heart failure are improved by administration of ACE inhibitors (and/or angiotensin receptor blockers), certain long-acting β-blockers (carvedilol or extended-release metoprolol), and aldosterone inhibitors (spironolactone or eplerenone).
Circulating AVP levels, often markedly increased in patients with severe heart failure, will increase ventricular afterload and are responsible for a defect in free water clearance that is commonly associated with hyponatremia.
Brain natriuretic peptide (BNP) is produced in the heart in response to myocyte distention. Elevated BNP concentration (>500 pg/mL) usually indicates heart failure, and measurement of BNP concentration can be used to distinguish between heart failure and lung disease as a cause of dyspnea. Recombinant BNP was developed as a vasodilator and inhibitor of the renin–angiotensin–aldosterone system for use in patients with severe decompensated heart failure, but outcomes were not improved with its use.
Ventricular hypertrophy can occur with or without dilation, depending on the type of stress imposed on the ventricle. When the heart is subjected to either pressure or volume overload, the initial response is to increase sarcomere length and optimally overlap actin and myosin. With time, ventricular muscle mass begins to increase in response to the abnormal stress.
In the volume-overloaded ventricle, the problem is an increase in diastolic wall stress. The increase in ventricular muscle mass is sufficient only to compensate for the increase in diameter: The ratio of the ventricular radius to wall thickness is unchanged. Sarcomeres replicate mainly in series, resulting in eccentric hypertrophy. Although ventricular EF remains depressed, the increase in end-diastolic volume can maintain normal at-rest stroke volume (and cardiac output).
The problem in a pressure-overloaded ventricle is an increase in systolic wall stress. In this case, sarcomeres mainly replicate in parallel, resulting in concentric hypertrophy: The hypertrophy is such that the ratio of myocardial wall thickness to ventricular radius increases. As can be seen from Laplace’s law, systolic wall stress can then be normalized. Ventricular hypertrophy, particularly that caused by pressure overload, usually results in progressive diastolic dysfunction. The most common reasons for isolated left ventricular hypertrophy are hypertension and aortic stenosis.
CASE DISCUSSION A Patient With a Short P–R Interval
A 38-year-old man is scheduled for endoscopic sinus surgery following a recent onset of headaches. He gives a history of having passed out at least once during one of these headaches. A preoperative electrocardiogram (ECG) is normal, except for a P–R interval of 0.116 s with normal P-wave morphology. What is the significance of the short P–R interval?
The P–R interval, which is measured from the beginning of atrial depolarization (P wave) to the beginning of ventricular depolarization (QRS complex), usually represents the time required for depolarization of both atria, the AV node, and the His–Purkinje system. Although the P–R interval can vary with heart rate, it is normally 0.12 to 0.2 s in duration. What is preexcitation?
Preexcitation usually refers to early depolarization of the ventricles by an abnormal conduction pathway from the atria. Rarely, more than one such pathway is present. The most common form of preexcitation is due to the presence of an accessory pathway (bundle of Kent) that connects one of the atria with one of the ventricles. This abnormal connection between the atria and ventricles allows electrical impulses to bypass the AV node (hence the term bypass tract). The ability to conduct impulses along the bypass tract can be quite variable and may be only intermittent or rate dependent. Bypass tracts can conduct in both directions, retrograde only (ventricle to atrium), or, rarely, anterograde only (atrium to ventricle). The name Wolff–Parkinson–White (WPW) syndrome is often applied to ventricular preexcitation associated with tachyarrhythmias. How does preexcitation shorten the P–R interval?
In patients with preexcitation, the normal cardiac impulse originating from the SA node is conducted simultaneously through the normal (AV nodal) and anomalous (bypass tract) pathways. Because conduction is more rapid in the anomalous pathway than in the AV nodal pathway, the cardiac impulse rapidly reaches and depolarizes the area of the ventricles where the bypass tract ends. This early depolarization of the ventricle is reflected by a short P–R interval and a slurred initial deflection (δ wave) in the QRS complex. The spread of the anomalous impulse to the rest of the ventricle is delayed because it must be conducted by ordinary ventricular muscle, not by the much faster Purkinje system. The remainder of the ventricle is then depolarized by the normal impulse from the AV node as it catches up with the preexcitation front. Although the P–R interval is shortened, the resulting QRS is slightly prolonged and represents a fusion complex of normal and abnormal ventricular depolarizations.
The P–R interval in patients with preexcitation depends on relative conduction times between the AV nodal pathway and the bypass pathway. If conduction through the former is fast, preexcitation (and the δ wave) is less prominent, and QRS will be relatively normal. If conduction is delayed in the AV nodal pathway, preexcitation is more prominent, and more of the ventricle will be depolarized by the abnormally conducted impulse. When the AV nodal pathway is completely blocked, the entire ventricle is depolarized by the bypass pathway, resulting in a very short P–R interval, a very prominent δ wave, and a wide, bizarre QRS complex. Other factors that can affect the degree of preexcitation include interatrial conduction time, the distance of the atrial end of the bypass tract from the SA node, and autonomic tone. The P–R interval is often normal or only slightly shortened with a left lateral bypass tract (the most common location). Preexcitation may be more apparent at fast heart rates because conduction slows through the AV node with increasing heart rates. Secondary ST-segment and T-wave changes are also common because of abnormal ventricular repolarization. What is the clinical significance of preexcitation?
Preexcitation occurs in approximately 0.3% of the general population. Up to 50% of affected persons develop paroxysmal tachyarrhythmias, typically paroxysmal supraventricular tachycardia (PSVT). Although most patients are otherwise normal, preexcitation can be associated with other cardiac anomalies, including Ebstein anomaly, mitral valve prolapse, and cardiomyopathies. Depending on its conductive properties, the bypass tract in some patients may predispose them to tachyarrhythmias and even sudden death. Tachyarrhythmias include PSVT, atrial fibrillation, and, less commonly, atrial flutter. Ventricular fibrillation can be precipitated by a critically timed premature atrial beat that travels down the bypass tract and catches the ventricle at a vulnerable period. Alternatively, very rapid conduction of impulses into the ventricles by the bypass tract during atrial fibrillation can rapidly lead to myocardial ischemia, hypoperfusion, and hypoxia and culminate in ventricular fibrillation.
Recognition of the preexcitation phenomenon is also important because its QRS morphology on the surface ECG can mimic bundle branch block, right ventricular hypertrophy, ischemia, myocardial infarction, and ventricular tachycardia (during atrial fibrillation). What is the significance of the history of syncope in this patient?
This patient should be evaluated preoperatively with electrophysiological studies, and may possibly require curative radiofrequency ablation of the bypass tract with antiarrhythmic drug therapy. Such studies can identify the location of the bypass tracts, reasonably predict the potential for malignant arrhythmias by programmed pacing, and assess the efficacy of antiarrhythmic therapy if curative ablation is not possible. Ablation is reported to be curative in over 90% of patients. A history of syncope may be ominous because it may indicate the ability to conduct impulses very rapidly through the bypass tract, leading to systemic hypoperfusion and perhaps predisposing the patient to sudden death. How do tachyarrhythmias generally develop?
Tachyarrhythmias develop as a result of either abnormal impulse formation or abnormal impulse propagation (reentry). Abnormal impulses result from enhanced automaticity, abnormal automaticity, or triggered activity. Usually, only cells of the SA node, specialized atrial conduction pathways, AV nodal junctional areas, and the His–Purkinje system depolarize spontaneously. Because diastolic repolarization (phase 4) is fastest in the SA node, other areas of automaticity are suppressed. Enhanced or abnormal automaticity in other areas, however, can usurp pacemaker function from the SA node and lead to tachyarrhythmias. Triggered activity is the result of either early after-depolarizations (phase 2 or 3) or delayed after-depolarizations (after phase 3). It consists of small-amplitude depolarizations that can follow action potentials under some conditions in atrial, ventricular, and His–Purkinje tissue. If these after-depolarizations reach threshold potential, they can result in an extrasystole or repetitive sustained tachyarrhythmias. Factors that can promote the formation of abnormal impulses include increased catecholamine levels, electrolyte disorders (hyperkalemia, hypokalemia, and hypercalcemia), ischemia, hypoxia, mechanical stretch, and drug toxicity (particularly digoxin).
The most common mechanism for tachyarrhythmias is reentry. Four conditions are necessary to initiate and sustain reentry (Figure 20–19): (1) two areas in the myocardium that differ in conductivity or refractoriness and that can form a closed electrical loop; (2) unidirectional block in one pathway (Figure 20–19A and B); (3) slow conduction or sufficient length in the circuit to allow recovery of the conduction block in the first pathway (Figure 20–19C); and (4) excitation of the initially blocked pathway to complete the loop (Figure 20–19D). Reentry is usually precipitated by a premature cardiac impulse. What is the mechanism of PSVT in patients with WPW syndrome?
If the bypass tract is refractory during anterograde conduction of a cardiac impulse, as during a critically timed atrial premature contraction (APC), and the impulse is conducted by the AV node, the same impulse can be conducted retrograde from the ventricle back into the atria via the bypass tract. The retrograde impulse can then depolarize the atrium and travel down the AV nodal pathway again, establishing a continuous repetitive circuit (circus movement). The impulse reciprocates between the atria and ventricles and conduction alternates between the AV nodal pathway and the bypass tract. The term concealed conduction is often applied because the absence of preexcitation during this arrhythmia results in a normal QRS that lacks a δ wave.
The circus movement less commonly involves anterograde conduction through the bypass tract and retrograde conduction through the AV nodal pathway. In such instances, the QRS has a δ wave and is completely abnormal; the arrhythmia can be mistaken for ventricular tachycardia. What other mechanisms may be responsible for PSVT?
In addition to the WPW syndrome, PSVT can be caused by AV reentrant tachycardia, AV nodal reentrant tachycardia, and SA node and atrial reentrant tachycardias. Patients with AV reentrant tachycardia have an extranodal bypass tract similar to patients with WPW syndrome, but the bypass tract conducts only retrograde; preexcitation and a δ wave are absent.
Functional differences in conduction and refractoriness may occur within the AV node, SA node, or atria; a large bypass tract is not necessary. Thus, the circus movement may occur on a smaller scale within the AV node, SA node, or atria, respectively. How does atrial fibrillation in patients with WPW syndrome differ from the arrhythmia in other patients?
Atrial fibrillation can occur when a cardiac impulse is conducted rapidly retrograde up into the atria and arrives to find different parts of the atria out of phase in recovery from the impulse. Once atrial fibrillation is established, conduction into the ventricles most commonly occurs through the bypass tract only; because of the accessory pathway’s ability to conduct very rapidly (unlike the AV nodal pathway), the ventricular rate is typically very rapid (180–300 beats/min). The majority of QRS complexes are abnormal, but periodic conduction of an impulse through the AV nodal pathway results in occasional normal-looking QRS complexes. Less commonly, impulses during atrial fibrillation are conducted mainly through the AV nodal pathway (resulting in mostly normal QRS complexes) or through both the bypass tract and the AV nodal pathway (resulting in a mixture of normal, fusion, and abnormal QRS complexes). As stated previously, atrial fibrillation in patients with WPW syndrome is a very dangerous arrhythmia. What anesthetic agents can safely be used in patients with preexcitation?
Few data are available comparing the use of different anesthetic agents or techniques in patients with preexcitation. Almost all the volatile and intravenous agents have been used. Volatile anesthetics increase antegrade refractoriness in both normal and accessory pathways. Propofol, opioids, and benzodiazepines seem to have little direct electrophysiological effects, but can alter autonomic tone, generally reducing sympathetic outflow. Factors that tend to cause sympathetic stimulation and increased cardiac automaticity are undesirable. Light anesthesia, hypercapnia, acidosis, and even transient hypoxia will activate the sympathetic system and are to be avoided. When patients with preexcitation are anesthetized for electrophysiological study and surgical ablation, opioids, propofol, and benzodiazepines may be the agents least likely to alter conduction characteristics. How are antiarrhythmic agents selected for tachyarrhythmias?
Most antiarrhythmic agents act by altering myocardial cell conduction (phase 0), repolarization (phase 3), or automaticity (phase 4). Prolongation of repolarization increases the refractoriness of cells. Many antiarrhythmic drugs also exert direct or indirect autonomic effects. Although antiarrhythmic agents are generally classified according to broad mechanisms of action or electrophysiological effects (Table 20–8), the most commonly used classification system is not perfect because some agents have more than one mechanism of action.
Selection of an antiarrhythmic agent generally depends on whether the arrhythmia is ventricular or supraventricular and whether acute control or chronic therapy is required. Intravenous agents are usually employed in the acute management of arrhythmias, whereas oral agents are reserved for chronic therapy (Table 20–9). Which agents are most useful for tachyarrhythmias in patients with WPW syndrome?
Cardioversion is the treatment of choice in hemodynamically compromised patients. Small doses of phenylephrine (100 mcg), together with vagal maneuvers (carotid massage if not contraindicated by carotid occlusive disease), help support arterial blood pressure and may terminate the arrhythmia. The most useful pharmacological agents are class Ia drugs (eg, procainamide). Procainamide increases the refractory period and decreases conduction in the accessory pathway. Moreover, class Ia drugs frequently terminate and can suppress the recurrence of PSVT and atrial fibrillation. Amiodarone is not recommended. Adenosine, verapamil, and digoxin are contraindicated during atrial fibrillation or flutter in these patients because they can dangerously accelerate the ventricular response. Both types of agents decrease conduction through the AV node, favoring conduction of impulses down the accessory pathway. The bypass tract is capable of conducting impulses into the ventricles much faster than the AV nodal pathway. Digoxin may also increase the ventricular response by shortening the refractory period and increasing conduction in accessory pathways. Although verapamil can terminate PSVT, its use in this setting may be hazardous because patients can subsequently develop atrial fibrillation or flutter. Moreover, atrial fibrillation may not be readily distinguishable from ventricular tachycardia in these patients if wide-QRS tachycardia develops.
A–D: The mechanism of reentry. See text for description.
TABLE 20–8Summary of antiarrhythmic drugs.1 ||Download (.pdf) TABLE 20–8 Summary of antiarrhythmic drugs.1
|Subclass, Drug ||Mechanism of Action ||Effects ||Clinical Applications ||Route, Pharmacokinetics, Toxicities, Interactions |
|CLASS 1A |
|Procainamide ||INa (primary) and IKr (secondary) blockade || |
Slows conduction velocity and pacemaker rate
Prolongs action potential duration and dissociates from INa channel with intermediate kinetics
Direct depressant effects on sinoatrial (SA) and atrioventricular (AV) nodes
Most atrial and ventricular arrhythmias
Drug of second choice for most sustained ventricular arrhythmias associated with acute myocardial infarction
Oral, IV, IM
Eliminated by hepatic metabolism to N-acetylprocainamide (NAPA) and renal elimination
NAPA implicated in torsades de pointes in patients with renal failure
Toxicity: Hypotension. Long-term therapy produces reversible lupus-related symptoms
Quinidine: Similar to procainamide but more toxic (cinchonism, torsades); rarely used in arrhythmias
Disopyramide: Similar to procainamide but significant antimuscarinic effects; may precipitate heart failure; not commonly used
|CLASS 1B |
|Lidocaine ||Sodium channel (INa) blockade || |
Blocks activated and inactivated channels with fast kinetics
Does not prolong and may shorten action potential
|Terminates ventricular tachycardias and prevents ventricular fibrillation after cardioversion || |
First-pass hepatic metabolism
Reduce dose in patients with heart failure or liver disease
Toxicity: Neurological symptoms
|Mexiletine: Orally active congener of lidocaine; used in ventricular arrhythmias, chronic pain syndromes |
|CLASS 1C |
|Flecainide ||Sodium channel (INa) blockade || |
Dissociates from channel with slow kinetics
No change in action potential duration
Supraventricular arrhythmias in patients with normal heart
Do not use in ischemic conditions (post-myocardial infarction)
Hepatic and kidney metabolism
Half-life ∼ 20 h
Propafenone: Orally active, weak β-blocking activity; supraventricular arrhythmias; hepatic metabolism
Moricizine: Phenothiazine derivative, orally active; ventricular arrhythmias, proarrhythmic. Withdrawn in USA.
|CLASS 2 |
|Propranolol ||β-Adrenoceptor blockade || |
Direct membrane effects (sodium channel block) and prolongation of action potential duration
Slows SA node automaticity and AV nodal conduction velocity
|Atrial arrhythmias and prevention of recurrent infarction and sudden death || |
Duration 4–6 h
Toxicity: Asthma, AV blockade, acute heart failure
Interactions: With other cardiac depressants and hypotensive drugs
|Esmolol: Short-acting, IV only; used for intraoperative and other acute arrhythmias |
|CLASS 3 |
|Amiodarone ||Blocks IKr, INa, ICa-L channels, β-adrenoceptors || |
Prolongs action potential duration and QT interval
Slows heart rate and AV node conduction
Low incidence of torsades de pointes
|Serious ventricular arrhythmias and supraventricular arrhythmias || |
Variable absorption and tissue accumulation • hepatic metabolism, elimination complex and slow
Toxicity: Bradycardia and heart block in diseased heart, peripheral vasodilation, pulmonary and hepatic toxicity
Hyper- or hypothyroidism
Interactions: Many, based on CYP metabolism
|Dofetilide ||IKr block ||Prolongs action potential, effective refractory period ||Maintenance or restoration of sinus rhythm in atrial fibrillation || |
Toxicity: Torsades de pointes (initiate in hospital)
Interactions: Additive with other QT-prolonging drugs
Sotalol: β-Adrenergic and IKr blocker, direct action potential prolongation properties, use for ventricular arrhythmias, atrial fibrillation
Ibutilide: Potassium channel blocker, may activate inward current; IV use for conversion in atrial flutter and fibrillation
Dronedarone: Amiodarone derivative; multichannel actions, reduces mortality in patients with atrial fibrillation
Vernakalant: Investigational in the United States, multichannel actions in atria, prolongs atrial refractoriness, effective in atrial fibrillation
|CLASS 4 |
|Verapamil ||Calcium channel (ICa-L type) blockade || |
Slows SA node automaticity and AV nodal conduction velocity
Decreases cardiac contractility
Reduces blood pressure
|Supraventricular tachycardias, hypertension, angina || |
Caution in patients with hepatic dysfunction
|Diltiazem: Equivalent to verapamil |
|Adenosine ||Activates inward rectifier IK • blocks ICa ||Very brief, usually complete AV blockade ||Paroxysmal supraventricular tachycardias || |
Duration 10–15 s
Toxicity: Flushing, chest tightness, dizziness
|Magnesium ||Poorly understood • interacts with Na+–K+–ATPase, K+, and Ca2+ channels ||Normalizes or increases plasma Mg2+ ||Torsades de pointes • digitalis-induced arrhythmias || |
Duration dependent on dosage
Toxicity: Muscle weakness in overdose
|Potassium ||Increases K+ permeability, K+ currents ||Slows ectopic pacemakers • slows conduction velocity in heart ||Digitalis-induced arrhythmias • arrhythmias associated with hypokalemia || |
Toxicity: Reentrant arrhythmias, fibrillation or arrest in overdose
TABLE 20–9Clinical pharmacological properties of antiarrhythmic drugs.1 ||Download (.pdf) TABLE 20–9 Clinical pharmacological properties of antiarrhythmic drugs.1