The sinoatrial (SA) node is the normal pacemaker of the heart and the origin of each normal heartbeat. The SA node is a collection of specialized myocytes near the site where the superior vena cava enters in the wall of the right atrium. Spontaneous depolarization of the SA node occurs, resulting in the generation of action potentials. Figure 4-5 illustrates the pathway by which excitation (depolarization) spreads through the heart. Action potentials from the SA node spread rapidly throughout the atria via gap junctions between adjacent myocytes.
Electrical conducting system of the heart. Sinoatrial node → atrial muscle → atrioventricular node → bundle of His → bundle branches → Purkinje fibers → ventricular muscle.
The atrioventricular (AV) node is the only electrical communication between the atria and the ventricles. It is characterized by very slow electrical conduction, ensuring that atrial contraction is completed before the ventricles are activated. The AV node is continuous with the ventricular conducting system, which consists of the atrioventricular bundle (bundle of His), the left and right bundle branches, and the Purkinje fiber system.
The ventricular conducting system is composed of columns of specialized myocytes containing a small amount of contractile protein. The large diameter of cells reduces electrical resistance and promotes rapid conduction. A thick connective tissue sheath insulates the ventricular conducting system, ensuring that the first electrical connection with working ventricular muscle occurs through Purkinje fibers. Action potentials spread rapidly through the ventricular muscle via gap junctions between the adjacent myocytes. The typical sequence of ventricular activation is from the left side of the ventricular septum near the apex of the heart, and then to the inner surface of the myocardium in both ventricles in the region of the apex. The general spread of excitation is from the inner (endo-) myocardium to the outer (epi-) myocardium and from the apex toward the base.
In Wolff-Parkinson-White syndrome, there is an accessory conduction pathway that creates a bidirectional link between the atria and the ventricles. A normal impulse that conducts from the atria down the AV node to the ventricles can travel up the accessory pathway to reexcite the atria. Alternatively, an atrial impulse can first conduct down the accessory pathway, depolarizing the ventricles, and then travel up the AV node (retrograde) and reactivate the atria. Either possibility can lead to paroxysmal supraventricular tachycardia, which manifests as palpitations, syncope, hypotension, and sometimes heart failure.
Ventricular Muscle Action Potential
Action potentials arriving at the ventricular muscle from the ventricular conducting system trigger the rapid spread of action potentials in all ventricular myocytes. The ventricular muscle action potential has a very long duration (250 ms). Figure 4-6 illustrates the following five phases of the ventricular muscle action potential, 0 through 4:
Phase 4 is the interval between action potentials when the ventricular muscles are at their stable resting membrane potential.
Phase 0 is the initial rapid upstroke that occurs immediately after stimulation. Membrane potential moves from its resting value of about −90 mV to a peak of about +30 mV during phase 0.
Phase 1 is a partial repolarization of the membrane potential from its peak value of +30 mV to about 0 mV.
Phase 2, also known as the plateau phase, is a dramatic slowing of repolarization.
Phase 3 is the repolarization of membrane potential back to the resting value.
Ventricular action potential. Phase 4 = stable resting membrane potential; phase 0 = rapid depolarization upon stimulation; phase 1 = partial repolarization; phase 2 = plateau phase; and phase 3 = repolarization. INa, Na+ current; ICa, Ca2+ current; IK, K+ current.
Figure 4-7 illustrates the SA node action potential. SA nodal cells are pacemakers because their membrane potential difference depolarizes spontaneously during phase 4, which is called the pacemaker potential or diastolic depolarization. The maximum membrane potential difference in pacemaker cells is about −60 mV, but there is no stable period of resting membrane potential. When the pacemaker potential reaches a threshold voltage of about −40 mV, the action potential is triggered in the cells of the SA node. When compared with ventricular muscle, phase 0 in the SA node is slow and the action potential duration is shorter. Action potential generation in the AV node is qualitatively the same as in the SA node but has a significantly slower phase 4 depolarization. Table 4-2 contrasts the ionic basis of nodal and ventricular muscle action potentials.
Nodal action potential. Phase 4 = unstable pacemaker potential; phase 0 = slow depolarization upon stimulation; and phase 3 = repolarization. If, nonselective cation current; ICa, Ca2+ current; IK, K+ current.
Table 4-2Ionic Currents Responsible for Ventricular Muscle and Nodal Action Potentials ||Download (.pdf) Table 4-2Ionic Currents Responsible for Ventricular Muscle and Nodal Action Potentials
|Location ||Phase 4 ||Phase 0 ||Phase 1 ||Phase 2 ||Phase 3 |
|Ventricular muscle ||Stable resting potential: ||INa ↑ (fast) || ||Plateau phase: ||Repolarization: |
|Sinoatrial and atrioventricular nodes ||Unstable pacemaker potential: ||ICa ↑ (slow) || || ||Repolarization: |
A knowledge of the ventricular action potential helps in the understanding of the mechanism of antiarrhythmic agents. There are four classes of antiarrhythmics, based on their site of action: class I, sodium channel blockers; class II, beta blockers; class III, potassium channel blockers; and class IV, calcium channel blockers. The SA node and AV node action potential upstroke (phase 4) is Ca2+ dependent, whereas the ventricular upstroke (phase 0) is Na+ dependent. As such, class I antiarrhythmics are effective in the treatment of ventricular ectopy (additional heart beats of ventricular origin), and class II and class IV antiarrhythmics are effective in slowing conduction in the SA and AV nodes.
The SA node is the normal pacemaker of the heart because it has the most rapid rate of phase 4 (diastolic) depolarization. A person is in normal sinus rhythm when cardiac excitation progresses from the SA node through the entire conduction pathway. The intrinsic rate of SA node firing is about 100 beats/min. Normal parasympathetic tone reduces the SA node firing rate to about 70 beats/min at rest. Endurance athletes have enhanced parasympathetic tone, which results in the classic finding of a slow resting heart rate in trained individuals. The AV node becomes the pacemaker if the SA node fails or transmission to the AV node fails. These patients are in nodal rhythm and typically have resting heart rates of 45–55 beats/min.
In patients with complete heart block (see normal and abnormal heart rhythm), there is no transmission through the AV node; the His-Purkinje fibers pace the heart between 20 and 40 beats/min. Slower pacemaker activity in distal parts of the conducting system allows the heart to continue beating if the SA node fails. However, these patients are likely to have bradycardia (slow heart rate) and reduced cardiac output. For example, sick sinus syndrome occurs when the SA node becomes fibrotic and loses its ability to spontaneously depolarize. Patients have bradycardia and symptoms of hypoperfusion such as dizziness, syncope, weakness, and fatigue. Abnormal heart rhythms can be diagnosed by observing an electrocardiogram (ECG).
The normal mechanical pumping cycle of the heart requires a single excitation event. Any additional action potentials spread rapidly through coupled myocardial cells and produce additional arrhythmias (inappropriate heart beats). If the ventricular rate is excessive, there is insufficient time between beats for the ventricles to fill.
Figure 4-8 shows that ventricular muscle cells have a long, effective (absolute) refractory period from the onset of phase 0 to midway through phase 3. This protects against circular (reentry) conduction, in which control by the pacemaker fails and each spread of excitation through the ventricles triggers the next. Treatment with drugs such as beta blockers and calcium channel blockers, which extend the refractory period, can be effective at preventing reentry arrhythmias. The long refractory period of the AV nodal cells also protects against conduction of rapid atrial arrhythmias to the ventricles. For example, in atrial fibrillation, the atrial rate is between 350 and 500 impulses per minute. Without the refractory properties of the AV node, the ventricular rate would correspond with the atrial rate, which would be incompatible with life.
Cardiac action potentials. Cardiac action potentials have long refractory periods (RP). No stimulus can produce another action potential during the effective refractory period.
Autonomic Regulation of Heart Rate
If the autonomic nerves to the heart are cut (such as may occur during a heart transplant), the spontaneous heart rate at rest is approximately 100 beats/min. Parasympathetic tone reduces the typical resting heart rate to approximately 70 beats/min, and parasympathetic stimulation reduces the heart rate further and produces a negative chronotropic effect. Parasympathetic nerves release acetylcholine, which acts via the muscarinic receptors on the nodal cells. The muscarinic receptor antagonist atropine can be used to treat symptomatic bradycardia. Atropine blocks parasympathetic tone, allowing sympathetic tone to continue unchecked. Sympathetic nerve stimulation or circulating catecholamines increase the heart rate and produce a positive chronotropic effect. Sympathetic nerves release norepinephrine, acting on the β1-adrenergic receptors. Figure 4-9 contrasts the parasympathetic and sympathetic nerve stimulation of the SA node, which underlies the effects on heart rate.
Effects of autonomic nerve stimulation on nodal action potentials. Parasympathetic (vagal) stimulation reduces the heart rate by hyperpolarizing the nodal cells and reducing the slope of pacemaker potentials. Sympathetic stimulation increases the heart rate by depolarizing the nodal cells and increasing the slope of pacemaker potentials.
Activation of the sympathetic nervous system occurs in response to stress. Signs include tachycardia as well as pale cool skin, sweating, and dilation of the pupils. It is important to identify the cause of sympathetic drive, which may be intrinsic or extrinsic. Examples of intrinsic activation include pain, fear, anxiety, or hypotension; examples of extrinsic activation include the use of drugs such as caffeine, cocaine, methamphetamines, or ephedrine.
The collective spread of action potentials through the myocytes produces small voltages that can be measured on the surface of the body with an ECG. A standard ECG is obtained by placing an electrode on each limb and at six specific locations on the anterior chest wall. In a lead, one electrode is regarded as the positive side of a voltmeter and another is the negative side. A lead reports changes in voltage difference between the positive and negative electrodes. By varying which electrode is regarded as positive or which is negative, a standard set of 12 leads provides a range of views of electrical events in the heart. Figure 4-10 illustrates the major waves on an ECG, together with standard intervals and segments and standard calibrations of time and voltage. Electrical activity in nodal and conducting tissue is not seen on an ECG because the amount of tissue is too small to produce measurable voltage differences at the body surface.
Electrocardiogram (ECG). Typical recording from lead II, showing ECG waves, segments, and intervals, and standard calibrations for time and voltage.
ECG waveforms are produced by momentary changes in voltage differences during the spread of cardiac excitation.
The P wave represents atrial depolarization.
The QRS complex is produced by ventricular depolarization.
The T wave results from ventricular repolarization.
Atrial repolarization is obscured by the QRS complex.
The QT interval is mostly determined by the duration of phase 2 of the ventricular action potential (Figure 4-6). A longer phase 2 is represented on the ECG as a prolonged QT interval, which may set up a dangerous form of ventricular tachycardia called torsade de pointes. Class III antiarrhythmic drugs cause a prolonged phase 2 of the action potential because repolarization is delayed when the K+ channels are blocked. Careful monitoring of the QT interval is a must when initiating therapy with a class III drug (e.g., amiodarone).
Heart muscle mass is depicted as amplitude on the ECG. For example, the P wave is smaller than the QRS complex because atria have less mass than ventricles. Left ventricular hypertrophy is identified if the sum of voltage deflections for the S wave in lead V1 and the R wave in leads V5 or V6 ≥ 35 mm. Similarly, right ventricular hypertrophy is characterized by an R wave that is larger than the S wave in V1.
ECG signals are vector quantities, since charge movement through the heart has both direction and magnitude. Two lead systems have been devised as follows (Table 4-3):
Table 4-3Placement and Polarity of Electrocardiogram Electrodes ||Download (.pdf) Table 4-3Placement and Polarity of Electrocardiogram Electrodes
|Lead System ||Lead Name ||+Ve Electrode ||-Ve (reference) Electrode |
|Frontal plane leads ||I ||LA ||RA |
| ||II ||LL ||RA |
| ||III ||LL ||LA |
| ||aVR ||RA ||LA & LL combined |
| ||aVL ||LA ||RA & LL combined |
| ||aVF ||LL ||RA & LA combined |
|Transverse plane precordial leads ||V1 ||Fourth intercostal space to the right of the sternum || |
| ||V2 ||Fourth intercostal space to the left of the sternum || |
| ||V4 ||Fifth intercostal space in the midclavicular line ||Virtual reference to center of heart |
| ||V3 ||Midway between V2 and V4 || |
| ||V6 ||Fifth intercostal space in the midaxillary line || |
| ||V5 ||Midway between V4 and V6 || |
The frontal (vertical) plane is defined by six limb leads.
The transverse plane is perpendicular to the frontal plane and is defined by six precordial chest leads.
Table 4-3 lists the placement of standard ECG electrodes. Every lead has a unique axis within its plane. Frontal plane leads are composed of three bipolar limb leads (I, II, and III), in which the positive electrode placed on one limb is compared to a negative electrode placed on another limb. These electrode connections to the left arm, the right arm, and the left leg form an equilateral triangle with the heart at its center, called Einthoven's triangle (Figure 4-11A). Three augmented unipolar limb leads (aVR, aVL, and aVF) are defined by using each limb electrode as a positive electrode referenced to a null point obtained by adding the potential from the other two limb leads.
Frontal plane electrocardiogram leads. A. Einthoven's triangle, formed by bipolar limb leads I, II, and III. Directions of the unipolar limb leads aVR, aVL, and aVF are also shown. B. Hexaxial reference circle, showing the axis of each frontal plane lead.
The frontal plane is a circle in which each lead occupies one axis. The hexaxial reference system produced by the six frontal plane leads is shown in Figure 4-11B. This system provides a means of describing the direction of an electrical vector produced by the spread of electrical activity in the heart. The direction of the mean QRS vector is used most often because it is affected by common pathology (e.g., ventricular hypertrophy; bundle branch block). Each precordial chest electrode is a positive electrode terminal and can be compared to the virtual center of the heart, estimated electronically from the average of the limb leads.
Figure 4-12 illustrates the concept of an electrical vector and how one may appear on different ECG leads. The ECG is an extracellular recording that views cells from the outside. Resting myocytes have a negative voltage on the inside of the cell membrane or, stated differently, they have a positive voltage on the outside of the cell membrane. A region of myocytes that has depolarized is negative on the outside when compared to neighboring cells at rest. This creates a voltage difference between adjacent regions, which is a vector quantity.
An electrical vector recorded by different electrocar leads. Adjacent areas of cells at different potentials produce a vector. A large positive recording in lead A is seen because the vector is parallel to lead A and directed at its positive terminal. A large negative recording is seen in lead B because the vector is parallel to lead B but directed at its negative terminal. No net signal is recorded in lead C because it is perpendicular to the vector.
Vectors are represented using an arrow to illustrate their size and direction. By convention, the head of the vector (arrow) points toward the positive voltage (toward tissue not yet depolarized). The average vector changes momentarily in size and direction, producing the waves seen on an ECG. All 12 leads simultaneously report the spread of excitation through the heart when viewed from different angles. The waveform is different on each lead because each lead has a different orientation to the heart.
A major event is recorded by a lead when the vector direction is parallel to the axis of the lead. No net deflection is recorded by a lead if the vector is perpendicular to the axis of the lead. This concept is used to estimate the direction of vectors by assessing the ECG. The largest net deflection occurs in the lead that is roughly parallel to the electrical event. If a lead shows no net deflection (i.e., the event is isoelectric), then the electrical vector is perpendicular to the axis of that lead. Knowledge of the orientation of leads in the frontal plane is necessary to estimate vector direction in this way.
Mean Electrical Axis of Ventricular Depolarization
In principle, the axis (vector direction) of any part of the ECG can be determined. The mean axis of ventricular depolarization is most commonly evaluated by analyzing the QRS complex. The mean QRS axis has a normal range of −30° to +90° on the hexaxial reference system. Axes in the range of −30° to −90° are termed left axis deviation; axes in the range of +90° to +150° are termed right axis deviation.
Ventricular hypertrophy is the thickening (or enlargement) of the myocardium and is a common cause of axis deviation. An increased left ventricular mass biases the direction of the net QRS vector toward the left. Similarly, patients with right ventricular hypertrophy usually have a right axis deviation. Left axis deviation can also occur when the abdominal contents physically push the heart up and to the left, such as occurs in patients who are obese or pregnant.
Mean electrical axis usually can be estimated from an ECG by inspection alone. Figure 4-13 shows an example of left axis deviation. The sum of all deflections (net deflection) in the QRS complex of lead aVR is near zero. The mean axis is, therefore, approximately perpendicular to this lead, corresponding to the axis of lead III. As expected, there is a large net QRS deflection recorded in lead III, confirming that the electrical vector in this case is roughly parallel to lead III (and perpendicular to aVR). Because the net deflection is negative in lead III, the QRS vector is directed at the negative end of lead III at an angle of approximately −60° on the hexaxial reference system.
Inspection method to assess the mean QRS axis (mean electrical axis of the heart).
Normal and Abnormal Heart Rhythm
An ECG is routinely used to record heart rate and rhythm. Figure 4-14 compares a normal lead II record with several common arrhythmias. In normal sinus rhythm, a P wave is followed at normal intervals by a QRS complex and a T wave (see Figure 4-14A). Heart rate, in beats/min, is calculated by dividing the R-R interval (expressed in seconds) into 60. Heart rate above 100 beats/min is described as tachycardia; a heart rate below 60 beats/min is described as bradycardia.
Electrocardiogram recordings of common arrhythmias.
A premature atrial beat is revealed when a P wave occurs earlier than expected and is followed by the usual QRS complex and T wave (see Figure 4-14B). Paroxysmal atrial tachycardia is a rapid run of heart beats that begins suddenly and ends abruptly; P waves precede each QRS complex, showing that beats originate in the atria (see Figure 4-14C). In atrial fibrillation (see Figure 4-14D), there is chaotic electrical activity; no P waves can be defined, and QRS complexes occur at irregular intervals, reflecting random depolarization of the AV node. The resulting pulse is classically described as “irregularly irregular.” In atrial fibrillation, stasis of blood often occurs in the atrial appendages due to the loss of atrial contraction. Anticoagulation therapy may be needed to counter the risk of thromboembolism.
Heart block is a group of abnormalities characterized by varying degrees of impaired conduction through the AV node.
In first-degree heart block, the PR interval is abnormally long at a normal heart rate, indicating delayed conduction through the AV node (see Figure 4-14E).
Second-degree heart block is characterized by intermittent failure of the AV node so that not every P wave is followed by a QRS complex. There are two types of second-degree heart block: Mobitz type I (Wenckebach) block is a benign rhythm whose origin is the AV node (see Figure 4-14F). It is characterized by progressive lengthening of the PR interval on consecutive beats, followed by a dropped QRS complex. Mobitz type II second-degree heart block is a more ominous rhythm and has its origin in the distal His-Purkinje system. It is characterized by dropped ventricular beats that are not preceded by PR interval lengthening (see Figure 4-14G). The block may persist for two or more beats, yielding an atrial to ventricular ratio of 2:1, 3:1, and so on. Type II heart block may progress quickly to complete heart block.
Third-degree (complete) heart block occurs when the atrial rhythm is completely dissociated from the ventricular rhythm (see Figure 4-14H). There is no relation between P waves and QRS-T complexes. Complete AV block may come and go. When a period of block begins, there is often an interval of 5–30 seconds before the ventricular conducting system takes over as the pacemaker. During this period, the patient faints due to lack of cerebral blood flow. This pattern of periodic fainting is called Stokes-Adams syndrome. Treatment of third-degree heart block includes implanting a pacemaker to maintain an adequate heart rate and blood pressure.
Arrhythmias that impact the timing and performance of ventricular contraction may arise from within the ventricles rather than being the result of abnormalities of atrial rhythm or AV node. Premature ventricular contractions (PVCs) occur with no preceding P wave (see Figure 4-14I). The origin of the ventricular excitation is within the ventricular conducting system or from a ventricular muscle focus. The QRS complex is often an irregular shape, reflecting a pattern of electrical spread that differs from a normal pacemaker source. Abnormal ventricular pacemakers, which are often damaged or unstable areas of ventricular myocardium, can drive ventricular tachycardia. This is a dangerous type of arrhythmia because the beating frequency may be too high to allow adequate ventricular filling. Ventricular tachycardia may degenerate into ventricular fibrillation associated with random chaotic electrical activity (see Figure 4-14J). Ventricular fibrillation is fatal within a short period of time due to lack of coordinated ventricular contraction.
PVCs are either asymptomatic or are sensed as palpitations. They occur in most of the normal population and are benign. However, in the setting of a current or past myocardial infarction (MI), PVCs may become more frequent. Two episodes of PVCs coupled together are known as couplets; three or more episodes of PVCs coupled together are known as ventricular tachycardia and are associated with increased mortality. The most common cause of death during an MI is fatal arrhythmia (ventricular fibrillation or ventricular tachycardia).
Arrhythmias are often caused by electrolyte abnormalities. For example, as plasma K+ concentration increases, hyperkalemia produces the following sequence of cardiotoxic effects: peaked T waves, prolonged PR interval, widening of the QRS complex, blockage of the AV node, loss of P waves, and eventual merging of the QRS complex with the T wave, which produces a “sine wave” pattern that can degenerate into ventricular fibrillation or asystole.