Unformatted text preview: Electrophysiology Normal Heart Rhythm
The rhythm of the heart is normally determined by a pacemaker site called the sinoatrial (SA) node located in the posterior wall of the right atrium near the superior vena cava. The SA node consists of specialized cells that undergo spontaneous generation of action potentials at a rate of 100-110 action potentials ("beats") per minute. This intrinsic rhythm is strongly influenced by autonomic nerves, with the vagus nerve being dominant over sympathetic influences at rest. This "vagal tone" brings the resting heart rate down to 60-80 beats/minute. The normal range for sinus rhythm is 60-100 beats/ minute. Sinus rates below this range are termed sinus bradycardia and sinus rates above this range are termed sinus tachycardia. The sinus rhythm normally controls both atrial and ventricular rhythm. Action potentials generated by the SA node spread throughout the atria, depolarizing this tissue and causing atrial contraction. The impulse then travels into the ventricles via the atrioventricular node (AV node). Specialized conduction pathways (bundle branches and Purkinje fibers) within the ventricle rapidly conduct the wave of depolarization throughout the ventricles to elicit ventricular contraction. Therefore, normal cardiac rhythm is controlled by the pacemaker activity of the SA node. Abnormal cardiac rhythms can occur if 1. the SA node fails to function normally (e.g., sinus bradycardia or tachycardia) 2. impulses are not conducted from the atria to the ventricles through the AV node (termed AV block) 3. abnormal conduction pathways are followed (e.g., accessory pathways between atria and ventricles) 4. other pacemaker sites within the atria or ventricles (e.g., ectopic pacemakers) trigger depolarization 1 Electrophysiology Normal Impulse Conduction
Sequence of Cardiac Electrical Activation
The action potentials generated by the SA node spread throughout the atria primarily by cell-to-cell conduction. There is some functional evidence for the existence of specialized conducting pathways within the atria (termed internodal tracts), although this is controversial. The conduction velocity of action potentials in the atrial muscle is about 0.5 m/sec. As the wave of action potentials depolarizes the atrial muscle, the cardiomyocytes contract by a process termed excitation-contraction coupling. Normally, the only pathway available for action potentials to enter the ventricles is through a specialized region of cells (atrioventricular node, or AV node) located in the inferior-posterior region of the interatrial septum. The AV node is a highly specialized conducting tissue (cardiac, not neural in origin) that slows the impulse conduction considerably (to about 0.05 m/ sec) thereby allowing sufficient time for complete atrial depolarization and contraction (systole) prior to ventricular depolarization and contraction. The impulses then enter the base of the ventricle at the Bundle of His and then follow the left and right bundle branches along the interventricular septum. These specialized fibers conduct the impulses at a very rapid velocity (about 2 m/sec). The 2 Electrophysiology bundle branches then divide into an extensive system of Purkinje fibers that conduct the impulses at high velocity (about 4 m/sec) throughout the ventricles. This results in depolarization of ventricular myocytes and ventricular contraction. The conduction system within the heart is very important because it permits a rapid and organized depolarization of ventricular myocytes that is necessary for the efficient generation of pressure during systole. The time (in seconds) to activate the different regions of the heart are shown in the figure to the right. Atrial activation is complete within about 0.09 sec (90 msec) following SA nodal firing. After a delay at the AV node, the septum becomes activated (0.16 sec). All the ventricular mass is activated by about 0.23 sec. Regulation of Conduction
The conduction of electrical impulses throughout the heart, and particularly in the specialized conduction system, is strongly influenced by autonomic nerve activity. Sympathetic activation increases conduction velocity in nodal and non-nodal tissues by increasing the slope of phase 0 of the action potentials. This leads to more rapid depolarization of adjacent cells. This positive dromotropic effect of sympathetic activation results from norepinephrine binding to beta-adrenoceptors, which increases intracellular cAMP. Therefore, drugs that block beta-adrenoceptors (betablockers) decrease conduction velocity and can produce AV block. Parasympathetic (vagal) activation decreases conduction velocity (negative dromotropy) in nodal and non-nodal tissues by decreasing the slope of phase 0 of the action potentials. This leads to slower depolarization of adjacent cells. Acetylcholine, released by the vagus nerve, binds to cardiac muscarinic receptors, which 3 Electrophysiology decreases intracellular cAMP. Excessive vagal activation can produce AV block. Drugs such as digitalis, which increase vagal activity to the heart, are used to reduce AV nodal conduction in patients that have atrial flutter or fibrillation. These atrial arrhythmias lead to excessive ventricular rate (tachycardia) that can be suppressed by partially blocking impulses being conducted through the AV node. Because conduction velocity depends on the rate of tissue depolarization, which is related to the slope of phase 0 of the action potential, conditions (or drugs) that alter phase 0 will affect conduction velocity. For example, conduction can be altered by changes in membrane potential, which can occur during myocardial ischemia and hypoxia. Cellular hypoxia leads to membrane depolarization, inhibition of fast Na+ channels, a decrease in the slope of phase 0, and a decrease in action potential amplitude in non-nodal cardiac muscle. These membrane changes result in a decrease in speed by which action potentials are conducted within the heart. Antiarrhythmic drugs such as quinidine (a Class IA antiarrhythmic) that block sodium channels and cause a decrease in conduction velocity in non-nodal tissue. Phase 0 action potentials at the AV node is not dependent on fast sodium channels, but instead are generated by the entry of calcium into the cell through slow-inward, L-type calcium channels. Blocking these channels with a calcium-channel blocker such as verapamil or diltiazem reduces the conduction velocity of impulses through the AV node and can produce AV block. Conduction Defects
If the conduction system becomes damaged or dysfunctional, as can occur during ischemic conditions or myocardial infarction, electrical conduction becomes impaired. This can have a number of consequences. First, activation of the heart will be delayed, and in some cases, the sequence of activation will be altered. This can seriously impair ventricular pressure development. Second, damage to the conducting system can precipitate tachyarrhythmias by reentry mechanisms. Click here to learn more about altered impulse conduction. 4 Electrophysiology Sinoatrial Node Action Potentials
Cells within the sinoatrial (SA) node are the primary pacemaker site within the heart. These cells are characterized as having no true resting potential, but instead generate regular, spontaneous action potentials. Unlike non-pacemaker action potentials in the heart, and most other cells that elicit action potentials (e.g., nerve cells, muscle cells), the depolarizing current is carried primarily by relatively slow, inward Ca++ currents instead of by fast Na+ currents. There are, in fact, no fast Na+ channels and currents operating in SA nodal cells. This results in a slower action potentials in terms of how rapid they depolarize. Therefore, these pacemaker action potentials are sometimes referred to as "slow response" action potentials. SA nodal action potentials are divided into three phases. Phase 4 is the spontaneous depolarization (pacemaker potential) that triggers the action potential once the membrane potential reaches threshold between -40 and -30 mV). Phase 0 is the depolarization phase of the action potential. This is followed by phase 3 repolarization. Once the cell is completely repolarized at about -60 mV, the cycle is spontaneously repeated. The changes in membrane potential during the different phases are brought about by changes in the movement of ions (principally Ca++ and K+, and to a lesser extent Na+) across the membrane through ion channels that open and close at different times during the action potential. When a channel is opened, there is increased electrical conductance (g) of specific ions through that ion channel. Closure of ion channels causes ion conductance to decrease. As ions flow through open channels, they generate electrical currents (i or I) that change the membrane potential. In the SA node, three ions are particularly important in generating the pacemaker action potential. The role of these ions in the different action potential phases are illustrated in the figure and described below: At the end of repolarization, when the membrane potential is very negative (about -60 mV), ion channels open that conduct slow, inward (depolarizing) Na+ currents. These currents are called "funny" currents and abbreviated as "If". These depolarizing currents cause the membrane potential to begin to spontaneously depolarize, thereby initiating Phase 4. As the membrane potential reaches about -50 mV, another type of channel opens. This channel is called 5 Electrophysiology transient or T-type Ca++ channel. As Ca++ enters the cell through these channels down its electrochemical gradient, the inward directed Ca++ currents further depolarize the cell. As the membrane continues to depolarize to about -40 mV, a second Ca++ channel opens. These are the so-called long-lasting, or L-type Ca++ channels. Opening of these channels causes more Ca++ to enter the cell and to further depolarize the cell until an action potential threshold is reached (usually between -40 and -30 mV). During Phase 4 there is also a slow decline in the outward movement of K+ as the K+ channels responsible for Phase 3 continue to close. This fall in K+ conductance (gK+) contributes to the pacemaker potential. Phase 0 depolarization is primarily caused by increased Ca++ conductance (gCa+ +) through the L-type Ca++ channels that began to open toward the end of Phase 4. The "funny" currents, and Ca++ currents through the T-type Ca++ channels, decline during this phase as their respective channels close. Because the movement of Ca++ through these channels into the cell is not rapid, the rate of depolarization (slope of Phase 0) is much slower than found in other cardiac cells (e.g., Purkinje cells). Repolarization occurs (Phase 3) as K+ channels open (increased gK+) thereby increasing the outward directed, hyperpolarizing K+ currents. At the same time, the L-type Ca++ channels close, gCa++ decreases, and the inward depolarizing Ca ++ currents diminish. During depolarization, the membrane potential (Em) moves toward the equilibrium potential for Ca++, which is about +134 mV. During repolarization, g'Ca++ (relative Ca++ conductance) decreases and g'K+ (relative K+ conductance) increases, which brings Em closer toward the equilibrium potential for K+, which is about -96 mV). Therefore, the action potential in SA nodal cells is primarily dependent upon changes in Ca++ and K+ conductances as summarized below: Em = g'K+ (-96 mV) + g'Ca++ (+134 mV)
Although pacemaker activity is spontaneously generated by SA nodal cells, the rate of this activity can be modified significantly by external factors such as by autonomic nerves, hormones, drugs, ions, and ischemia/hypoxia. It is important to note that action potentials described for SA nodal cells are very similar to those found in the atrioventrcular (AV) node. Therefore, action potentials in the AV node, like the SA node, are determined primarily by changes in slow inward Ca++ and K+ currents, and do not involve fast Na+ currents. AV node action potentials also have intrinsic pacemaker activity produced by the same ion currents as described above for SA nodal cells. 6 Electrophysiology Regulation of Pacemaker Activity
The SA node displays intrinsic automaticity (spontaneous pacemaker activity) at a rate of 100-110 action potentials ("beats") per minute. This intrinsic rhythm is primarily influenced by autonomic nerves, with vagal influences being dominant over sympathetic influences at rest. This "vagal tone" reduces the resting heart rate down to 60-80 beats/min. The SA node is predominantly innervated by efferent branches of the right vagus nerves, although some innervation from the left vagus is often observed. Experimental denervation of the right vagus to the heart leads to an abrupt increase in SA nodal firing rate if the resting heart rate is below 100 beats/min. A similar response is noted when a drug such as atropine is administered. This drug blocks vagal transmission at the SA node by antagonizing the muscarinic receptors that bind to acetylcholine, which is the neurotransmitter released by the vagus nerve. Parasympathetic (vagal) activation, which releases acetylcholine (ACh) onto the SA node, decreases pacemaker rate by increasing gK+ and decreasing slow inward gCa++ and gNa+; the pacemaker current (If) is suppressed. These ionic conductance changes decrease the slope of phase 4 of the action potential, thereby increasing the time required to reach threshold. Vagal activity also hyperpolarizes the pacemaker cell during Phase 4, which results in a longer time to reach threshold voltage. The rate of SA nodal firing can be altered by: 1. changes in autonomic nerve activity (sympathetic and vagal) To increase heart rate, the autonomic nervous system increases sympathetic outflow to the SA node, with concurrent inhibition of vagal tone. Inhibition of vagal tone is necessary for the sympathetic nerves to increase heart rate because vagal influences inhibit the action of sympathetic nerve activity. Sympathetic activation, which releases norepinephrine (NE), increases pacemaker rate by decreasing gK+ and increasing slow inward gCa++ and gNa+; the pacemaker current (If) is enhanced. These changes increase the slope of phase 4 so that the pacemaker potential more rapidly reaches the threshold for action potential generation. 7 Electrophysiology 2. circulating hormones Pacemaker activity is also altered by hormones. For example, hyperthyroidism induces tachycardia and hypothyroidism induces bradycardia. Circulating epinephrine causes tachycardia by a mechanism similar to norepinephrine released by sympathetic nerves. Changes in the serum concentration of ions, particularly potassium, can cause changes in SA nodal firing rate. Hyperkalemia induces bradycardia or can even stop SA nodal firing. Hypokalemia increases the rate of phase 4 depolarization and causes tachycardia. It apparently does this by decreasing gK during phase 4. Cellular hypoxia (usually due to ischemia) depolarizes the membrane potential causing bradycardia; severe hypoxia completely stops pacemaker activity. Various drugs used as antiarrhythmics also affect SA nodal rhythm. Calciumchannel blockers, for example, cause bradycardia by inhibiting the slow inward Ca++ currents during phase 4 and phase 0. Drugs affecting autonomic control or autonomic receptors (e.g., beta-blockers, muscarinic antagonists) directly or indirectly alter pacemaker activity. Digitalis causes bradycardia by increasing parasympathetic (vagal) activity on the SA node; however, at toxic concentrations, digitalis increases automaticity and therefore can cause tachyarrhythmias. This toxic effect is related to the inhibitory effects of digitalis on the membrane Na+/K+-ATPase, which leads to cellular depolarization, increased intracellular calcium, and changes in ion conductances. 3. serum ion concentrations 4. cellular hypoxia 5. Drugs Pacemaker activity is influenced dramatically by age. The maximal heart rate that can be achieved in an individual is estimated by Maximal Heart Rate @ 220 beats/min age in years
Therefore a 20-year-old person will have a maximal heart rate of about 200 beats/min, and this will decrease to about 170 beats/min when the person is 50 years of age. This maximal heart rate is genetically determined and cannot be modified by exercise training or by external factors. 8 Electrophysiology Non-Pacemaker Action Potentials
Atrial myocytes, ventricular myocytes and Purkinje cells are examples of nonpacemaker action potentials in the heart. Because these action potentials undergo very rapid depolarization, they are sometimes referred to as "fast response" action potentials. Unlike pacemaker cells found in nodal tissue within the heart, non-pacemaker cells have a true resting membrane potential (phase 4) that remains near the equilibrium potential for K+ (EK). The resting membrane potential is very negative during phase 4 (about -90 mV) because potassium channels are open (K+ conductance [gK+] and K+ currents [IK] are high). As shown in the figure, phase 4 is associated with K+ currents, in which positive potassium ions are leaving the cell and thereby making the membrane potential more negative inside. At the same time, fast sodium channels and (L-type) slow calcium channels are closed. When these cells are rapidly depolarized to a threshold voltage of about -70 mV (e.g., by an action potential in an adjacent cell), there is a rapid depolarization (phase 0) that is caused by a transient increase in fast Na+-channel conductance (gNa+) through fast sodium channels. This increases the inward directed, depolarizing Na+ currents (INa) that are responsible for the generation of these "fast-response" action potentials (see above figure). At the same time sodium channels open, gK+ and outward directed K+ currents fall as potassium channels close. These two conductance changes move the membrane potential away from EK (which is negative) and closer toward the equilibrium potential for sodium (ENa), which is positive. Phase 1 represents an initial repolarization that is caused by the opening of a special type of transient outward K+ channel (Kto), which causes a short-lived, hyperpolarizing outward K+ current (IKto). However, because of the large increase in slow inward gCa++ occurring at the same time and the transient nature of IKto, the repolarization is delayed and there is a plateau phase in the action potential (phase 2). This inward calcium movement is through long-lasting (L-type) calcium channels that open up when the membrane potential depolarizes to about -40 mV. This plateau phase prolongs the 9 Electrophysiology action potential duration and distinguishes cardiac action potentials from the much shorter action potentials found in nerves and skeletal muscle. Repolarization (phase 3) occurs when gK+ (and therefore IK) increases, along with the inactivation of Ca++ channels (decreased gCa++). Therefore, the action potential in non-pacemaker cells is primarily determined by relative changes in fast Na+, slow Ca++ and K+ conductances and currents. As described under the discussion on membrane potentials and summarized in the following relationship and in the figure to the right, the membrane potential (Em) is determined by the relative conductances of the major ions distributed across the cell membrane. When g'K+ is high and g'Na+ and g'Ca++ are low (phases 3 and 4), the membrane potential will be more negative. When g'K+ is low and g'Na+ and/or g'Ca++ are high, the membrane potential will be more positive (phases 0, 1 and 2). Em = g'K+ (-96 mV) + g'Na+ (+50 mV) + g'Ca++ (+134 mV) These fast-response action potentials in non-nodal tissue are altered by antiarrhythmic drugs that block specific ion channels. Sodium-channel blockers such as quinidine inactivate fast-sodium channels and reduce the rate of depolarization (decrease the slope of phase 0). Calcium-channel blockers such as verapamil and diltiazem affect the plateau phase (phase 2) of the action potential. Potassium-channel blockers delay repolarization (phase 3) by blocking the potassium channels that are responsible for this phase. Effective Refractory Period
Once an action potential is initiated, there is a period of time comprising phases 0, 1, 2, and part of phase 3 that a new action potential cannot be initiated. This is termed the effective refractory period (ERP) or the absolute refractory period (ARP) of the cell. During the ERP, stimulation of the cell by an adjacent cell undergoing depolarization does not produce new, propagated action potentials. The ERP acts as a protective mechanism in the heart by preventing multiple, compounded action potentials from 10 Electrophysiology occurring (i.e., it limits the frequency of depolarization and therefore heart rate). This is important because at very high heart rates, the heart would be unable to adequately fill with blood and therefore ventricular ejection would be reduced. Many antiarrhythmic drugs alter the ERP, thereby altering cellular excitability. For example, drugs that block potassium channels (e.g., amiodarone, a Class III antiarrhythmic) delays phase 3 repolarization and increases the ERP. Drugs that increase the ERP can be particularly effective in abolishing reentry currents that lead to tachyarrhythmias. Transformation of non-pacemaker into pacemaker cells
It is important to note that non-pacemaker action potentials can change into pacemaker cells under certain conditions. For example, if a cell becomes hypoxic, the membrane depolarizes, which closes fast Na+ channels. At a membrane potential of about 50 mV, all the fast Na+ channels are inactivated. When this occurs, action potentials can still be elicited; however, the inward current are carried by Ca++ (slow inward channels) exclusively. These action potentials resemble those found in pacemaker cells located in the SA node, and can sometimes display spontaneous depolarization and automaticity. This mechanism may serve as the electrophysiological mechanism behind certain types of ectopic beats and arrhythmias, particularly in ischemic heart disease and following myocardial infarction. 11 Electrophysiology Arrhythmias
What is an arrhythmia?
The rhythm of the heart is normally generated and regulated by pacemaker cells within the sinoatrial (SA) node, which is located within the wall of the right atrium. SA nodal pacemaker activity normally governs the rhythm of the atria and ventricles. Normal rhythm is very regular, with minimal cyclical fluctuation. Furthermore, atrial contraction is always followed by ventricular contraction in the normal heart. When this rhythm becomes irregular, too fast (tachycardia) or too slow (bradycardia), or the frequency of the atrial and ventricular beats are different, this is called an arrhythmia. The term "dysrhythmia" is sometimes used and has a similar meaning. How common are arrhythmias?
About 14 million people in the USA have arrhythmias (5% of the population). The most common disorders are atrial fibrillation and flutter. The incidence is highly related to age and the presence of underlying heart disease; the incidence approaches 30% following open heart surgery. What are the clinical symptoms?
Patients may describe an arrhythmia as a palpitation or fluttering sensation in the chest. For some types of arrhythmias, a skipped beat might be sensed because the subsequent beat produces a more forceful contraction and a thumping sensation in the chest. A "racing" heart is another description. Proper diagnosis of arrhythmias requires an electrocardiogram, which is used to evaluate the electrical activity of the heart. Depending on the severity of the arrhythmia, patients may experience dyspnea (shortness of breath), syncope (fainting), fatigue, heart failure symptoms, chest pain or cardiac arrest. What causes arrhythmias?
A frequent cause of arrhythmia is coronary artery disease because this condition results in myocardial ischemia or infarction. When cardiac cells lack oxygen, they become depolarized, which lead to altered impulse formation and/or altered impulse conduction. The former concerns changes in rhythm that are caused by changes in the automaticity of pacemaker cells or by abnormal generation of action potentials at sites other than the SA node (termed ectopic foci). Altered impulse conduction is usually associated with complete or partial block of electrical conduction within the heart. Altered impulse conduction commonly results in reentry, which can lead to tachyarrhythmias. Changes in cardiac structure that accompany heart failure (e.g., dilated or hypertrophied cardiac chambers), can also precipitate arrhythmias. Finally, many different types of drugs (including antiarrhythmic drugs) as well as electrolyte disturbances (primarily K+ and Ca+ +) can precipitate arrhythmias. What are the consequences of arrhythmias?
Arrhythmias can be either benign or more serious in nature depending on the hemodynamic consequence of the arrhythmia and the possibility of evolving into a lethal 12 Electrophysiology arrhythmia. Occasional premature ventricular complexes (PVCs), while annoying to a patient, are generally considered benign because they have little hemodynamic effect. Consequently, PVCs if not too frequent, are generally not treated. In contrast, ventricular tachycardia is a serious condition that can lead to heart failure, or worse, to ventricular fibrillation and death. How are arrhythmias treated?
When arrhythmias require treatment, they are are treated with drugs that suppress the arrhythmia. These drugs are called antiarrhythmic drugs. There are many different types of antiarrhythmic drugs and many different mechanisms of action. Most of the drugs affect ion channels that are involved in the movement of sodium, calcium and potassium ions in and out of the cell. These drugs include mechanistic classes such as sodiumchannel blockers, calcium-channel blockers and potassium-channel blockers. By altering the movement of these important ions, the electrical activity of the cardiac cells (both pacemaker and non-pacemaker cells) is altered, hopefully in a manner that suppresses arrhythmias. Other drugs affect autonomic influences on the the heart, which may be stimulating or aggravating arrhythmias. Among these drugs are betablockers. More details on drug therapy and specific drugs can be obtained by clicking here. 13 Electrophysiology Altered Impulse Formation
The normal pacemaker site for the heart is located within the SA node. Cells within this pacemaker region have an intrinsic firing rate that is modulated primarily by changes in autonomic nerve activity. If there is a high level of vagal tone on the SA node, then this will cause sinus bradycardia (an sinus rate <60 beats/min). Conversely, an abnormally high level of sympathetic tone on the SA node will cause sinus tachycardia (a sinus rate >100 beats/min). In a condition called sick sinus syndrome, the SA nodal firing rate alternates between bradycardia and normal rhythm. Abnormal impulse formation can be caused by the expression of ectopic pacemaker sites within the heart. These are sites outside of the SA node that can spontaneously depolarize and thereby produce atrial and/or ventricular action potentials independent of SA nodal firing. This can occur when the SA node ceases to operate as the dominant pacemaker site (e.g., when the SA node is damaged), or in the presence of normal SA nodal function. One mechanism by which this can occur is the transformation of normal, non-pacemaker action potentials (e.g., in Purkinje cells or myocytes) into pacemaker action potentials. This can occur when a cell becomes hypoxic, which leads to membrane depolarization. As a cell becomes progressively depolarized from -90 mV to -50 mV, fast Na+ channels become progressively inactivated. Inactivated Na+ channels cannot open and participate in the initial depolarization (phase 0) of the action potential. At a membrane potential of about 50 mV, all the fast Na+ channels are inactivated. When this occurs, action potentials can still be elicited; however, the inward current is carried by Ca++ (slow inward channels) exclusively. These action potentials resemble those found in pacemaker cells located in the SA node, and sometimes display spontaneous depolarization and automaticity. This mechanism may serve as the electrophysiological mechanism behind certain types of ectopic beats and arrhythmias, particularly in ischemic heart disease and following myocardial infarction. Triggered Activity
Triggered activity occurs when abnormal action potentials are triggered by a preceding action potential, and can result in either atrial or ventricular tachycardia. The abnormal impulses are seen as spontaneous (yet triggered) depolarizations that occur during either phase 3 or 4 of an action potential (called "afterdepolarizations"). Triggered activity is more likely to occur when the action potential duration is abnormally long, such as occurs in some patients with a genetic defect that produces a prolonged action potential manifested as a long Q-T interval on the electrocardiogram (long Q-T syndrome). Drugs that prolong the action potential duration, such as potassium-channel blockers (Class III antiarrhythmics), can precipitate triggered activity. Afterdepolarizations can be either early or delayed. Early afterdepolarizations occur during late phase 2 or phase 3 and can lead to a salvo of several rapid action potentials or a prolonged series of action potentials. This form of triggered activity is more likely to occur when the action 14 Electrophysiology potential duration is increased. Therefore, drugs that decrease action potential duration (e.g., lidocaine) are often effective against tachyarrhythmias generated by this mechanism. Calcium channel blockers, by decreasing gCa++, can also be effective in their treatment. Delayed afterdepolarizations occur in late phase 3 or early phase 4 when the action potential is nearly or fully repolarized. The mechanism is poorly understood; however, this type of arrhythmia is found to be associated with high intracellular Ca++ concentrations as occurs with digitalis toxicity or excessive catecholamine stimulation. The triggered impulse can lead to a series of rapid depolarizations (i.e., a tachyarrhythmia). 15 Electrophysiology Altered Impulse Conduction
Abnormal conduction of impulses within the heart can lead to arrhythmias. The most common pathophysiologic mechanism for abnormal conduction results from localized or regional depolarization due to hypoxia caused by impaired coronary blood flow. Depolarization decreases the action potential amplitude and rate of depolarization (phase 0 slope is decreased), both of which decrease the velocity of action potential conduction or completely stop the conduction of action potentials (i.e., conduction block). Conduction blocks can also be caused, especially at the AV node, by excessive vagal activation or because of drugs that reduce conduction such as beta-blockers and calcium-channel blockers. Conduction blocks can occur at the AV node, bundle of His, or bundle branches as shown in the figure. There are three categories of conduction blocks: AV block, bundle branch block, and hemiblock. When there is an AV block, impulses originating in the SA node cannot enter the ventricles. This type of block can occur either at the AV node, at the common bundle of His, or when both bundle branches are blocked. When this occurs, a pacemaker site distal to the block will become the new pacemaker for the heart. These secondary pacemaker sites generally have an intrinsic rate (30-50 impulses/min depending on the site), which is considerably slower than the SA node. Therefore, an AV conduction block will lead to ventricular bradycardia. When either the left or right bundle branch is blocked (bundle branch block), impulses still travel from the atria to the ventricles so there is no complete block and the ventricles will still be driven by the SA node. However, the sequence and timing of ventricular depolarization will be altered (see below). A hemiblock occurs when left anterior or posterior fascicle of the left bundle branch becomes blocked. When the conduction block is not a complete AV block (e.g., left bundle branch block), electrical impulses can travel along alternate conduction pathways to depolarize the ventricles. When this occurs, it takes longer for the ventricles to depolarize. This is manifested as an increase in the duration of the QRS complex, and a change in its shape. Sometimes, the abnormal conduction pathways can cause a self-perpetuating, circular movement of electrical activation. This is termed reentry and is a major cause of ventricular and supraventricular tachycardias. 16 Electrophysiology Electrocardiogram (EKG, ECG)
As the heart undergoes depolarization and repolarization, the electrical currents that are generated spread not only within the heart, but also throughout the body. This electrical activity generated by the heart can be measured by an array of electrodes placed on the body surface. The recorded tracing is called an electrocardiogram (ECG, or EKG). A "typical" ECG tracing is shown to the right. The different waves that comprise the ECG represent the sequence of depolarization and repolarization of the atria and ventricles. The ECG is recorded at a speed of 25 mm/sec, and the voltages are calibrated so that 1 mV = 10 mm in the vertical direction. Therefore, each small 1-mm square represents 0.04 sec (40 msec) in time and 0.1 mV in voltage. Because the recording speed is standardized, one can calculate the heart rate from the intervals between different waves. P wave
The P wave represents the wave of depolarization that spreads from the SA node throughout the atria, and is usually 0.08 to 0.1 seconds (80-100 ms) in duration. The brief isoelectric (zero voltage) period after the P wave represents the time in which the impulse is traveling within the AV node (where the conduction velocity is greatly retarded) and the bundle of His. Atrial rate can be calculated by determining the time interval between P waves. Click here to see how atrial rate is calculated. The period of time from the onset of the P wave to the beginning of the QRS complex is termed the P-R interval, which normally ranges from 0.12 to 0.20 seconds in duration. This interval represents the time between the onset of atrial depolarization and the onset of ventricular depolarization. If the P-R interval is >0.2 sec, there is an AV conduction block, which is also termed a first-degree heart block if the impulse is still able to be conducted into the ventricles. QRS complex
The QRS complex represents ventricular depolarization. Ventricular rate can be calculated by determining the time interval between QRS complexes. Click here to see how ventricular rate is calculated. 17 Electrophysiology The duration of the QRS complex is normally 0.06 to 0.1 seconds. This relatively short duration indicates that ventricular depolarization normally occurs very rapidly. If the QRS complex is prolonged (> 0.1 sec), conduction is impaired within the ventricles. This can occur with bundle branch blocks or whenever a ventricular foci (abnormal pacemaker site) becomes the pacemaker driving the ventricle. Such an ectopic foci nearly always results in impulses being conducted over slower pathways within the heart, thereby increasing the time for depolarization and the duration of the QRS complex. The shape of the QRS complex in the above figure is idealized. In fact, the shape changes depending on which recording electrodes are being used. The shape will also change when there is abnormal conduction of electrical impulses within the ventricles. The figure to the right summarizes the nomenclature used to define the different components of the QRS complex. ST segment
The isoelectric period (ST segment) following the QRS is the time at which the entire ventricle is depolarized and roughly corresponds to the plateau phase of the ventricular action potential. The ST segment is important in the diagnosis of ventricular ischemia or hypoxia because under those conditions, the ST segment can become either depressed or elevated. T wave
The T wave represents ventricular repolarization and is longer in duration than depolarization (i.e., conduction of the repolarization wave is slower than the wave of depolarization). Sometimes a small positive U wave may be seen following the T wave (not shown in figure at top of page). This wave represents the last remnants of ventricular repolarization. Inverted or prominent U waves indicates underlying pathology or conditions affecting repolarization. Q-T interval
The Q-T interval represents the time for both ventricular depolarization and repolarization to occur, and therefore roughly estimates the duration of an average ventricular action potential. This interval can range from 0.2 to 0.4 seconds depending upon heart rate. At high heart rates, ventricular action potentials shorten in duration, which decreases the Q-T interval. Because prolonged Q-T intervals can be diagnostic for susceptibility to certain types of tachyarrhythmias, it is important to determine if a given Q-T interval is excessively long. In practice, the Q-T interval is expressed as a "corrected Q-T (QTc)" by taking the Q-T interval and dividing it by the square root of the 18 Electrophysiology R-R interval (interval between ventricular depolarizations). This allows an assessment of the Q-T interval that is independent of heart rate. Normal corrected Q-Tc intervals are less than 0.44 seconds. There is no distinctly visible wave representing atrial repolarization in the ECG because it occurs during ventricular depolarization. Because the wave of atrial repolarization is relatively small in amplitude (i.e., has low voltage), it is masked by the much larger ventricular-generated QRS complex. ECG tracings recorded simultaneous from different electrodes placed on the body produce different characteristic waveforms. To learn where ECG electrodes are placed, CLICK HERE. 19 Electrophysiology Action Potentials
Many cells in the body have the ability to undergo a transient depolarization and repolarization that is either triggered by external mechanisms (e.g., motor nerve stimulation of skeletal muscle or cell-to-cell depolarization in the heart) or by intracellular, spontaneous mechanisms (e.g., cardiac pacemaker cells). There are two general types of cardiac action potentials. Non-pacemaker action potentials, also called "fast response" action potentials because of their rapid depolarization, are found throughout the heart except for the pacemaker cells. The pacemaker cells generate spontaneous action potentials that are also termed "slow response" action potentials because of their slower rate of depolarization. These are found in the sinoatrial and atrioventricular nodes of the heart. Both types of action potentials in the heart differ considerably from action potentials found in neural and skeletal muscle cells. One major difference is in the duration of the action potentials. In a typical nerve, the action potential duration is about 1 ms. In skeletal muscle cells, the action potential duration is approximately 2-5 ms. In contrast, the duration of cardiac action potentials range from 200 to 400 ms. Another difference between cardiac and nerve and muscle action potentials is the role of calcium ions in depolarization. In nerve and muscle cells, the depolarization phase of the action potential is caused by an opening of sodium channels. This also occurs in non-pacemaker cardiac cells. However, in cardiac pacemaker cells, calcium ions are involved in the initial depolarization phase of the action potential. In nonpacemaker cells, calcium influx prolongs the duration of the action potential and produces a characteristic plateau phase. 20 Electrophysiology Hemodynamic Consequences of Arrhythmias
Bradycardia, whether of atrial or ventricular origin, decreases cardiac output and thereby decreases arterial pressure. The reduced pressure can result in syncope (i.e., fainting) and other symptoms related to hypotension. Tachycardia of atrial or ventricular origin reduces stroke volume and cardiac output particularly when the ventricular rate is greater than 160 beats/min. The stroke volume becomes reduced because of decreased ventricular filling time and decreased ventricular filling (preload) at high rates of contraction. Furthermore, if the tachyarrhythmia is associated with abnormal ventricular conduction, the synchrony and therefore effectiveness of ventricular contraction will be impaired leading to reduced ejection. Another consequence of tachycardia is increased myocardial oxygen demand. This can cause angina (chest pain), particularly in patients having underlying coronary artery disease. Finally, chronic states of tachycardia can lead to systolic heart failure. In fact, a commonly used animal model for studying dilated cardiomyopathy is to induce ventricular failure by rapidly pacing the ventricular for a few weeks. Atrial fibrillation abolishes the contribution of atrial contraction to ventricular filling. Normally, under low, resting heart rates, atrial contractions account for about 10% of ventricular filling. However, during exercise when heart rate is elevated and ventricular filling time is reduced, atrial contraction can contribute up to 40% of ventricular filling. Therefore, atrial fibrillation generally has relatively minor hemodynamic consequence at rest, but can significantly limit normal increases in ventricular stroke volume and cardiac output during exercise. This may cause shortness of breath (exertional dyspnea) and impaired perfusion of active muscles, which will limit exercise capacity. Furthermore, in some cardiac pathologies such as ventricular hypertrophy in which ventricular compliance is reduced, atrial contraction contributes significantly to ventricular filling even at rest. Therefore, in these patients, atrial fibrillation can significantly effect resting cardiac output. Of major concern with atrial fibrillation is the increased risk of thrombus formation within the atria and the release of these thrombi into the pulmonary or systemic circulation, which can lead to pulmonary embolism or stroke. For this reason, patients with atrial fibrillation are commonly placed on anticoagulants such as coumadin. Atrial fibrillation also produces ventricular tachycardia because more impulses pass through the AV node. This is often treated with drugs (e.g., digoxin, calcium-channel blockers, beta-blockers) to reduce conduction velocity through the AV node, and thereby reduce ventricular rate. Ventricular fibrillation causes cardiac output to go to zero, and therefore leads to death unless it is quickly converted to a rhythm compatible with sustaining life. 21 Electrophysiology Abnormal Rhythms - Definitions
General Terms: Normal sinus rhythm - heart rhythm controlled by sinus node at a rate of 60-100 beats/min; each P wave followed by QRS and each QRS preceded by a P wave. Bradycardia - a heart rate that is lower than normal. Tachycardia - a heart rate that is higher than normal. Paroxysmal - an arrhythmia that suddenly begins and ends. Sinus bradycardia - low sinus rate <60 beats/min. Sinus tachycardia - high sinus rate of 100-180 beats/min as occurs during exercise or other conditions that lead to increased SA nodal firing rate. Sick sinus syndrome - a disturbance of SA nodal function that results in a markedly variable rhythm (cycles of bradycardia and tachycardia). Atrial tachycardia - a series of 3 or more consecutive atrial premature beats occurring at a frequency >100/min; usually due to abnormal focus within the atria and paroxysmal in nature, therefore appearance of P wave is altered in different ECG leads. This type of rhythm includes paroxysmal atrial tachycardia (PAT). Atrial flutter - sinus rate of 250-350 beats/min. Atrial fibrillation - uncoordinated atrial depolarizations. Junctional escape rhythm - SA node suppression can result in AV nodegenerated rhythm of 40-60 beats/min (not preceded by P wave). AV nodal blocks - a conduction block within the AV node (or occasionally in the bundle of His) that impairs impulse conduction from the atria to the ventricles. Specific Arrhythmias: First-degree AV nodal block - the conduction velocity is slowed so that the P-R interval is increased to greater than 0.2 seconds. Can be caused by enhanced vagal tone, digitalis, beta-blockers, calcium channel blockers, or ischemic damage. Second-degree AV nodal block - the conduction velocity is slowed to the point where some impulses from the atria cannot pass through the AV node. This can result in P waves that are not followed by QRS complexes. For example, 1 or 2 P waves may 22 Electrophysiology occur alone before one is followed by a QRS. When the QRS follows the P wave, the P-R interval is increased. In this type of block, the ventricular rhythm will be less than the sinus rhythm. Third-decree AV nodal block - conduction through the AV node is completely blocked so that no impulses are able to be transmitted from the atria to the ventricles. QRS complexes will still occur (escape rhythm), but they will originate from within the AV node, bundle of His, or other ventricular regions. Therefore, QRS complexes will not be preceded by P waves. Furthermore, there will be complete asynchrony between the P wave and QRS complexes. Atrial rhythm may be completely normal, but ventricular rhythm will be greatly reduced depending upon the location of the site generating the ventricular impulse. Ventricular rate typically range from 30 to 40 beats/min. Supraventricular tachycardia (SVT) - usually caused by reentry currents within the atria or between ventricles and atria producing high heart rates of 140-250; the QRS complex is usually normal width, unless there are also intraventricular conduction blocks (e.g., bundle branch block). Ventricular premature beats (VPBs) - caused by ectopic ventricular foci; characterized by widened QRS; often referred to as a premature ventricular complex, or PVC. Ventricular tachycardia (VT) - high ventricular rate caused by aberrant ventricular automaticity (ventricular foci) or by intraventricular reentry; can be sustained or non-sustained (paroxysmal); usually characterized by widened QRS (>0.14 sec); rates of 100 to 280 beats/min; life-threatening. Ventricular flutter - very rapid ventricular depolarizations >250/min; sine wave appearance; leads to fibrillation. Ventricular fibrillation - uncoordinated ventricular depolarizations; leads to death if not quickly converted to a normal rhythm or at least a rhythm compatible with life. 23 Electrophysiology Standard Limb Leads (Bipolar)
Bipolar recordings utilize standard limb lead configurations depicted at the right. By convention, lead I has the positive electrode on the left arm, and the negative electrode on the right arm, and therefore measures the potential difference between the two arms. In this and the other two limb leads, an electrode on the right leg serves as a reference electrode for recording purposes. In the lead II configuration, the positive electrode is on the left leg and the negative electrode is on the right arm. Lead III has the positive electrode on the left leg and the negative electrode on the left arm. These three bipolar limb leads roughly form an equilateral triangle (with the heart at the center) that is called Einthoven's triangle in honor of Willem Einthoven who developed the electrocardiogram in 1901. Whether the limb leads are attached to the end of the limb (wrists and ankles) or at the origin of the limb (shoulder or upper thigh) makes no difference in the recording because the limb can simply be viewed as a long wire conductor originating from a point on the trunk of the body. Based upon universally accepted ECG rules, a wave a depolarization heading toward the left arm gives a positive deflection in lead I because the positive electrode is on the left arm. Maximal positive ECG deflection occurs in lead I when a wave of depolarization travels parallel to the axis between the right and left arms. If a wave of depolarization heads away from the left arm, the deflection is negative. Also by these rules, a wave of repolarization moving away from the left arm is recorded as a positive deflection. Similar statements can be made for leads II and III in which the positive electrode is located on the left leg. For example, a wave of depolarization traveling toward the left leg produces a positive deflection in both leads II and III because the positive electrode for both leads is on the left leg. A maximal positive deflection is recorded in lead II when the depolarization wave travels parallel to the axis between the right arm and left leg. Similarly, a maximal positive deflection is obtained in lead III when the depolarization wave travels parallel to the axis between the left arm and left leg. If the three limbs of Einthoven's triangle (assumed to be equilateral) are broken apart, collapsed, and superimposed over the heart, then the positive electrode for lead I is said to be at zero degrees relative to the heart (along the horizontal axis) (see figure at right). Similarly, the positive electrode for lead II will be +60 relative to the heart, and the positive electrode for lead III will be +120 relative to the heart as shown to the right. This new construction of the electrical axis is called the axial reference system. With this system, a wave of depolarization traveling at +60 produces the greatest positive deflection in lead II. A wave of depolarization oriented +90 relative to the heart produces equally positive deflections in both lead II and III. In this latter example, lead I 24 Electrophysiology shows no net deflection because the wave of depolarization is heading perpendicular to the 0, or lead I, axis (see ECG rules). For a heart with a normal ECG and a mean electrical axis of +60, the standard limb leads will appear as follows: Augmented Limb Leads (Unipolar)
In addition to the three bipolar limb leads described above, there are three augmented unipolar limb leads. These are termed unipolar leads because there is a single positive electrode that is referenced against a combination of the other limb electrodes. The positive electrodes for these augmented leads are located on the left arm (aVL), the right arm (aVR), and the left leg (aVF). In practice, these are the same electrodes used for leads I, II and III. (The ECG machine does the actual switching and rearranging of the electrode designations). The three augmented leads, along with the three standard bipolar limb leads, are depicted as shown to the right using the axial reference system. The aVL lead is at -30 relative to the lead I axis; aVR is at -150 and aVF is at +90. It is very important to learn which lead is associated with each axis. 25 Electrophysiology The three augmented unipolar leads, coupled with the three bipolar leads, constitute the six limb leads of the ECG. These leads record electrical activity along a single plane, termed the frontal plane relative to the heart. Using the axial reference system and these six leads, it is simple to define the direction of an electrical vector at any given instant in time. If a wave of depolarization is spreading from right-toleft along the 0 axis, then lead I will show the greatest positive amplitude. If the direction of the electrical vector for depolarization is directed downwards (+90), then aVF will show the greatest positive deflection. If a wave of depolarization is moving from left-to-right at +150, then aVL will show the greatest negative deflection according to the rules for ECG interpretation. For a heart with a normal ECG and mean electrical axis of +60, the augmented leads will appear as follows: 26 Electrophysiology Volume Conductor Principles and ECG Rules of Interpretation
The electrocardiogram uses electrodes on the surface of the body to measure the electrical activity of the heart. It is possible to place electrodes on the body surface and measure cardiac potentials because the body acts as a conductor of the electrical currents generated by the heart. What do these electrodes actually measure? If a piece of living ventricular muscle is placed in a bath containing a salt solution to conduct electrical currents, and electrodes are placed in the bath on either side of the muscle, no potential difference would be recorded between the two electrodes when the muscle is in its polarized, resting state (top panel of figure at right). The reason for this is that the outside of the cells is positive relative to the inside because the resting membrane potential is be about -90 mV; therefore, no currents will flow along the surface of the muscle and through the bath. If the left side of the muscle is stimulated electrically to induce self-propagating action potentials, a wave of depolarization would sweep across the muscle from left-to-right (lower panel). Midway through this depolarization process, cells on the left (depolarized cells) would be negative on the outside relative to the inside, while nondepolarized cells on the right of the muscle would still be polarized (positive on the outside). There would now exist a potential difference between the positive and negative electrodes. By convention, a wave of depolarization heading toward the positive electrode is recorded as a positive voltage (upward deflection in the recording). After the wave of depolarization sweeps across the entire muscle mass, all the cells on the outside are negative, and once again, no potential difference would exist between the two electrodes. The entire process of depolarization and repolarization is depicted in the animated model to the right, which is representative of the electrical events that occur in the atria. In the resting, polarized state, no potential difference is measured between the positive and negative electrodes (i.e., isoelectric - flat red line). When the left side of the tissue becomes depolarized (representing firing of the SA node), a wave of depolarization begins to spread across the atria. During this time, some of the muscle mass temporarily remains positive on the outside (polarized) and while some is negative (depolarized); thus, there is a separation of charges which causes a potential difference between the two electrodes. Because the wave of depolarization is moving toward the positive electrode, by convention, a positive voltage (upward deflection) is recorded. 27 Electrophysiology The voltage reaches its maximal positive value when half the tissue is depolarized. Once the entire atrial mass is depolarized (all cells negative on outside), there is no longer be a potential difference and the voltage is zero just as it was in the polarized state. When repolarization occurs, starting first with the left side ( SA nodal region) then moving across the atria, there will once again be both positive and negative charges on the surface of the atria, but this time, the negative charges will be closest to the positive electrode. The wave of repolarization sweeping across the atria away from the negative electrode and toward the positive electrode causes, by convention, a negative voltage (downward deflection) to occur. Finally, when all of the cells are repolarized, the measured voltage difference will once again be zero until another wave of depolarization occurs. A similar process occurs within the ventricles with one major difference: repolarization normally occurs in a direction opposite to depolarization. In other words, the last cells in the ventricle to depolarize are the first to repolarize. This results in a positive recording as the ventricles repolarize as shown in the animated model to the right. Several important observations and rules emerge from these volume conductor considerations: 1. A wave of depolarization traveling toward a positive electrode results in a positive deflection in the ECG trace. 2. A wave of depolarization traveling away from a positive electrode results in a negative deflection. 3. A wave of repolarization traveling toward a positive electrode results in a negative deflection. 4. A wave of repolarization traveling away from a positive electrode results in a positive deflection. 5. A wave of depolarization or repolarization traveling perpendicular to an electrode axis results in a biphasic deflection of equal positive and negative voltages (i.e., no net deflection). 6. The instantaneous amplitude of the measured potentials depends upon the orientation of the positive electrode relative to the mean electrical vector. 7. The voltage amplitude is directly related to the mass of tissue undergoing depolarization or repolarization. The first four rules are derived from the volume conductor model described above. The fifth rule is also based on volume conductor principles and could be modeled by placing the positive and negative electrodes midway on the top and bottom surfaces of the tissue instead of on the ends. In this case, the positive electrode would first measure a positive voltage as the wave of depolarization transverse the tissue from the left edge to the midpoint (toward the electrode), and then the electrode would measure a negative voltage as the wave moved away from the electrode to the right edge. The sixth rule takes into consideration that at any given point in time during depolarization in the atria or ventricles there are many separate waves of depolarization traveling in different directions relative to the positive electrode. The recording by the electrode reflects the 28 Electrophysiology average, instantaneous direction and magnitude (i.e., mean electrical vector) for all of the individual depolarization waves. The seventh rule simply states that the amplitude of the wave recorded by the ECG is directly related to the mass of the muscle undergoing depolarization or repolarization. For example, when the mass of the left ventricle is increased by hypertrophy, the voltage amplitude of the QRS complex, which represents ventricular depolarization, is increased in certain leads. 29 Electrophysiology Ventricular Depolarization and the Mean Electrical Axis
Sequence of Ventricular Depolarization
The mean electrical axis is the average of all the instantaneous mean electrical vectors occurring sequentially during depolarization of the ventricles. The figure to the right depicts the sequence of depolarization within the ventricles. The septum and free left and right ventricular walls are shown. In this model, each of the four vectors is depicted as originating from the top of the interventricular septum just below the AV node. The electrode placement represents lead II. During ventricular activation, impulses are first conducted down the left and right bundle branches on either side the septum. This causes the septum to depolarize from left-toright as depicted by vector 1 (Panel A). This vector is heading slightly away from the positive electrode (to the right of a line perpendicular to the lead axis) and therefore will record a small negative deflection (Q wave of the QRS). About 20 milliseconds later, the mean electrical vector points downward toward the apex (vector 2), and is heading toward the positive electrode (Panel B). This will produce a very tall positive deflection (R wave of the QRS). After another 20 milliseconds later, the mean vector is pointing toward the left arm and anterior chest as the free wall of the ventricle depolarizes from the endocardial to the epicardial surface (vector 3, Panel C). This vector will record a small positive voltage in lead II. Finally, the last regions to depolarize will result in vector 4 (Panel D), which will cause a slight negative deflection (S wave) of the QRS. 30 Electrophysiology The shape of the QRS complex is different for each of the limb leads because each of the leads will "see" the sequence of depolarization vectors from a different perspective (see axial reference system). The animated figure to the right shows how the QRS complex appears for leads aVF and aVL. The positive electrodes for these two leads are at +90 and -30, respectively. In this illustration, the mean electrical axis (see below) is about +45. Note that aVF shows a large net positive QRS. There is no Q wave because septal depolarization is not directed away from the lead (see ECG rules). The R wave is very positive because early ventricular depolarization is largely directed toward this lead. The S wave is also present because the terminal depolarization of the upper wall of the left ventricle is directed away from aVF. In contrast, aVL shows an initial Q wave (septal depolarization is directed away from the lead) followed by a moderately positive R wave. The Mean Electrical Axis
In the above illustration, the mean electrical axis will be the sum of all of the mean electrical vectors. The mean electrical axis is depicted by the red arrow in the figure above and in the figure to the right, which is the same figure superimposed upon the axial reference system. In this example, the mean electrical axis is approximately +30. The mean electrical axis for the heart normally lies between -30 and +90. (Some textbooks say the normal range is 0 to +90.) Less than -30 (or less than 0) is termed a left axis deviation and greater than +90 is termed a right axis deviation. Axis deviations can be caused by increased cardiac muscle mass (e.g., left ventricular hypertrophy), changes in the sequence of ventricular activation (e.g., conduction defects), or because of ventricular regions being incapable of being activated (e.g., infarcted tissue). 31 Electrophysiology The mean electrical axis corresponds to the axis that is perpendicular to the lead axis that has the smallest net QRS amplitude (net amplitude = positive minus negative deflection voltages of QRS complex). In the above figure, lead III would have the smallest net amplitude (the ECG would be biphasic with equal positive and negative deflections). The mean electrical axis, therefore, is perpendicular to lead III, which is 120 minus 90, or approximately +30 in this example. Leads I and II will have equally positive QRS deflections. Lead aVR would have the greatest negative deflection. To determine the mean electrical axis from the ECG, find the lead axis that has a biphasic (equally positive and negative QRS deflections - i.e., no net deflection), then find the lead axis that is perpendicular (90) to the biphasic lead and that has a positive net deflection. In the six limb leads in the example below, aVL is biphasic. The positive perpendicular axis to aVL is +60. Therefore, the mean electrical axis is +60, which is normal. 32 Electrophysiology Ion Channels
The cell membrane is permeable to a number of ions, the most important of which are Na+, K+, Ca++ and Cl-. These ions pass across the membrane through specific ion channels that can open (become activated) and close (become inactivated). Therefore, these channels are said to be gated channels. Their opening and closing can occur in response to 1. voltage changes (voltage gated channels) 2. activation of receptors (receptor gated channels) 3. specific ions and chemical ligands Cardiac cells can have several different channels for a given ion. For example, there are many different types of potassium channels that play an important role in resting membrane potential and in action potentials. It is the opening and closing of ion channels that alters specific ion conductances in a manner that determines resting potentials and generates action potentials. For example, when an action potential is elicited in a cardiomyocyte, sodium channels transiently open and potassium channels close, which leads to depolarization. Shortly thereafter, the sodium channels close and calcium channels open to maintain a depolarized state. This is followed by inactivation of the calcium channels and a reopening of the potassium channels, which leads to membrane repolarization. The following table summarizes some of the important ion channels that are found in cardiac and vascular smooth muscle cells. CHANNEL CHARACTERISTICS Sodium Channels Fast Na+ Phase 0 depolarization of non-pacemaker cardiac action potentials "Funny" pacemaker current (If) in cardiac nodal tissue Slow Na+ Potassium Channels Inward rectifier (Iir or IK1) Maintains phase 4 negative potential in cardiac cells Contributes to phase 1 of non-pacemaker cardiac action potentials Phase 3 repolarization of cardiac action potentials Transient outward (Ito) Delayed rectifier (IKr) ATP-sensitive (IK, ATP) 33 Electrophysiology KATP channels; inhibited by ATP; therefore, open when ATP decreases during hypoxia; in vascular smooth muscle, adenosine removes the ATP inhibition and opens these channels, producing vasodilation Activated by acetylcholine; Gi-protein coupled Open in response to Ca++ influx in vascular smooth muscle Acetylcholine-activated (IK, ACh) Calcium-activated (IK, Ca or BKCa) Calcium Channels L-type (ICa-L) Slow inward, long-lasting current; phase 2 non-pacemaker cardiac action potentials and phases 4 and 0 of SA and AV nodal cells; important in vascular smooth muscle contraction Transient current that contributes to phase 4 pacemaker currents in SA and AV nodal cells T-type (ICa-T) - 34 Electrophysiology Determining Heart Rate from the Electrocardiogram
The term "heart rate" normally refers to the rate of ventricular contractions. However, because there are circumstances in which the atrial and ventricular rates differ (e.g., second and third degree AV block), it is important to be able to determine both atrial and ventricular rates. This is easily done by examining an ECG rhythm strip, which is usually taken from Lead II. In the example below, there are four numbered R waves, each of which is preceded by a P wave. Therefore, the atrial and ventricular rates will be the same because there is a one-to-one correspondence. Atrial rate can be determined by measuring the time intervals between P waves (P-P intervals). Ventricular rate can be determined by measuring the time intervals between the QRS complexes, which is done by looking at the R-R intervals. There are different short-cut methods that can be used to calculate rate, all of which assume a recording speed of 25 mm/sec. One method is to divide 1500 by the number of small squares between two R waves. For example, the rate between beats 1 and 2 in the above tracing is 1500/22, which equals 68 beats/min. Alternatively, one can divide 300 by the number of large squares (red boxes in this diagram), which is 300/4.4 (68 beats/min). Another method, which gives a rough approximation, is the "count off" method. Simply count the number of large squares between R waves with the following rates: 300 - 150 - 100 - 75 - 60. For example, if there are three large boxes between R waves, then the rate is 100 beats/min. One must extrapolate, however, between boxes. Atrial rate can be determined like the ventricular rate, but using the P waves. Remember, if the heart in in sinus rhythm and there is a one-to-one correspondence between P waves and QRS completes, then the atrial rate will be the same as ventricular rate. In the above examples, the ventricular rate was determined based on the interval between the first two beats. However, it is obvious that the rate would have been faster had it been calculated using beats 2 and 3 (104 beats/min) because because of a premature atrial beat, and slower if it had been calculated between beats 3 and 4 (52 beats/min). This illustrates an important point when calculating rate between any given pair of beats. If the rhythm is not steady, it is important to determine a time-averaged rate over a longer interval (e.g., over ten seconds or longer). For example, because the recording time scale is 25 mm/sec, if there are 12.5 beats in 10 seconds, the rate will be 75 beats/min. 35 Electrophysiology Control of Heart Rate
Heart rate is normally determined by the pacemaker activity of the sinoatrial node (SA node) located in the posterior wall of the right atrium. The SA node exhibits automaticity that is determined by spontaneous changes in Ca++, Na+, and K+ conductances. This intrinsic automaticity, if left unmodified by neurohumoral factors, exhibits a spontaneous firing rate of 100-115 beats/min. This intrinsic firing rate decreases with age. Heart rate is decreased below the intrinsic rate primarily by activation of the vagus nerve innervating the SA node. Normally, at rest, there is significant vagal tone on the SA node so that the resting heart rate is between 60 and 80 beats/min. This vagal influence can be demonstrated by administration of atropine, a muscarinic receptor antagonist, which leads to a 20-40 beats/min increase in heart rate depending upon the initial level of vagal tone. For heart rate to increase above the intrinsic rate, there is both a withdrawal of vagal tone and an activation of sympathetic nerves innervating the SA node. This reciprocal change in sympathetic and parasympathetic activity permits heart rate to increase during exercise, for example. Heart rate is also modified by circulating catecholamines acting via b1-adrenoceptors located on SA nodal cells. Heart rate is also modified by changes in circulating thyroxin (thyrotoxicosis causes tachycardia) and by changes in body core temperature (hyperthermia increases heart rate). SA nodal dysfunction can lead to sinus bradycardia, sinus tachycardia, or sick-sinus syndrome. The maximal heart rate that can be achieved in an individual is estimated by Maximal Heart Rate @ 220 beats/min age in years
Therefore a 20-year-old person will have a maximal heart rate of about 200 beats/min, and this will decrease to about 170 beats/min when the person is 50 years of age. This maximal heart rate is genetically determined and cannot be modified by exercise training or by external factors. 36 ...
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This note was uploaded on 04/18/2008 for the course PHYS 1010 taught by Professor Thompson during the Fall '07 term at New York Medical College.
- Fall '07