Electrical activation of the heart normally originates in the sinoatrial (SA) node, the predominant pacemaker. Other subsidiary pacemakers in the atrioventricular (AV) node, specialized conducting system, and muscle may initiate electrical activation if the SA node is dysfunctional or suppressed. Typically, subsidiary pacemakers discharge at a slower rate and, in the absence of an appropriate increase in stroke volume, may result in tissue hypoperfusion.
Spontaneous activation and contraction of the heart are a consequence of the specialized pacemaking tissue in these anatomic locales. As described in Chap. 231, action potentials in the heart are regionally heterogeneous. The action potentials in cells isolated from nodal tissue are distinct from those recorded from atrial and ventricular myocytes (Fig. 232-1). The complement of ionic currents present in nodal cells results in a less negative resting membrane potential compared with atrial or ventricular myocytes. Electrical diastole in nodal cells is characterized by slow diastolic depolarization (phase 4), which generates an action potential as the membrane voltage reaches threshold. The action potential upstrokes (phase 0) are slow compared with atrial or ventricular myocytes, being mediated by calcium rather than sodium current. Cells with properties of SA and AV nodal tissue are electrically connected to the remainder of the myocardium by cells with an electrophysiologic phenotype between that of nodal cells and that of atrial or ventricular myocytes. Cells in the SA node exhibit the most rapid phase 4 depolarization and thus are the dominant pacemakers in a normal heart.
Action potential profiles recorded in cells isolated from sinoatrial or atrioventricular nodal tissue compared with those of cells from atrial or ventricular myocardium. Nodal cell action potentials exhibit more depolarized resting membrane potentials, slower phase 0 upstrokes, and phase 4 diastolic depolarization.
Bradycardia results from a failure of either impulse initiation or impulse conduction. Failure of impulse initiation may be caused by depressed automaticity resulting from a slowing or failure of phase 4 diastolic depolarization (Fig. 232-2), which may result from disease or exposure to drugs. Prominently, the autonomic nervous system modulates the rate of phase 4 diastolic depolarization and thus the firing rate of both primary (SA node) and subsidiary pacemakers. Failure of conduction of an impulse from nodal tissue to atrial or ventricular myocardium may produce bradycardia as a result of exit block. Conditions that alter the activation and connectivity of cells (e.g., fibrosis) in the heart may result in failure of impulse conduction.
Schematics of nodal action potentials and the currents that contribute to phase 4 depolarization. Relative increases in depolarizing L- (ICa-L) and T- (ICa-T) type calcium and pacemaker currents (If) along with a reduction in repolarizing inward rectifier (IK1) and delayed rectifier (IK) potassium currents result in depolarization. Activation of ACh-gated (IKACh) potassium current and beta blockade slow the rate of phase 4 and decrease the pacing rate. (Modified from J Jalife et al: Basic Cardiac Electrophysiology for the Clinician, Blackwell Publishing, 1999.
SA node dysfunction and AV conduction block are the most common causes of pathologic bradycardia. SA node dysfunction may be difficult to distinguish from physiologic sinus bradycardia, particularly in the young. SA node dysfunction increases in frequency between the fifth and sixth decades of life and should be considered in patients with fatigue, exercise intolerance, or syncope and sinus bradycardia. Transient AV block is common in the young and probably is a result of the high vagal tone found in up to 10% of young adults. Acquired and persistent failure of AV conduction is decidedly rare in healthy adult populations, with an estimated incidence of ~200/million population per year.
Permanent pacemaking is the only reliable therapy for symptomatic bradycardia in the absence of extrinsic and reversible etiologies such as increased vagal tone, hypoxia, hypothermia, and drugs (Table 232-1). Approximately 50% of the 150,000 permanent pacemakers implanted in the United States and 20–30% of the 150,000 of those in Europe were implanted for SA node disease.
Table 232–1. Etiologies of SA Node Dysfunction
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Table 232–1. Etiologies of SA Node Dysfunction
|Autonomic||Sick-sinus syndrome (SSS)|
|Carotid sinus hypersensitivity ||Coronary artery disease (chronic and acute MI) |
|Vasovagal (cardioinhibitory) stimulation||Inflammatory|
|Beta blockers||Myocarditis (including viral)|
|Calcium channel blockers||Rheumatic heart disease|
|Digoxin||Collagen vascular diseases|
|Antiarrhythmics (class I and III)||Lyme disease|
|Clonidine (other sympatholytics)||Congenital heart disease|
|Lithium carbonate||TGA/Mustard and Fontan repairs |
|Narcotics (methadone) ||Chest trauma|
|Hypothyroidism||AD SSS, OMIM #163800 (15q24-25)|
|Sleep apnea Hypoxia||AR SSS, OMIM #608567 (3p21)|
|Endotracheal suctioning (vagal maneuvers)||SA node disease with myopia, OMIM 182190|
|Hypothermia||Kearns-Sayre syndrome, OMIM #530000|
|Increased intracranial pressure||Myotonic dystrophy|
|Type 1, OMIM #160900 (19q13.2-13.3) |
|Type 2, OMIM #602668 (3q13.3-q24) |
|Friedreich's ataxia, OMIM #229300 9q13, 9p23-p11)|
Structure and Physiology of the Sa Node
The SA node is composed of a cluster of small fusiform cells in the sulcus terminalis on the epicardial surface of the heart at the right atrial–superior vena caval junction, where they envelop the SA nodal artery. The SA node is structurally heterogeneous, but the central prototypic nodal cells have fewer distinct myofibrils than does the surrounding atrial myocardium, no intercalated disks visible on light microscopy, a poorly developed sarcoplasmic reticulum, and no T-tubules. Cells in the peripheral regions of the SA node are transitional in ...