Electrical Activity of Heart

6.3.1 Basic Mechanisms of Membrane

Potential

All the cells in the body maintain an electrical potential difference that can be measured across their plasma mem­brane which is called “membrane potential.” The intracellular fluid has more of K+ ions (140 mmol/L) and less of Na+ ions (14 mmol/L), whereas there is higher concentration of Na⁺ ions (142 mmol/L) and lower concentration of K⁺ ions (5 mmol/L) in the interstitial fluid.

The following are the three major factors contributing to the membrane potential:

1. Differential permeability of the membrane to diffusion of ions: The resting membrane is 50-100 times more permeable to K⁺ ions than to Na⁺ ions. Therefore, posi­tively charged K⁺ ions are allowed to diffuse out of the cell through non-gated leak channels down their concen­tration gradient (i.e., from inside of the cell to the outside).

2. Na⁺-K⁺-ATPasepump: Cell membranes have an energy­requiring pump, which pumps three Na⁺ ions out of the cell and two K⁺ ions into the cell against their concentra­tion gradient simultaneously.

3. Trapped anions inside the cell: Many intracellular anions are too large molecules to move outwards through the plasma membrane. Hence, they are trapped within the cell and are attracted to the inner surface of the cell membrane by the accumulated positive cations just on the outer side of the cell.

6.3.2 Cardiac Action Potential

All the living cells are excitable to stimuli. However, nerve and muscle cells are highly excitable cells than other cells.

Fig. 6.2 Action potential in a cardiac muscle cell. The depolarization occurs due to the opening of the (1) fast sodium channels, (2) slow sodium­calcium channels, and (3) repolarization due to potassium channels.

Action potential is the rapid changes in the membrane poten­tial from its normal negativity to positive potential that last for a period of few milliseconds, and then it returns back to its original resting potential level. The resting membrane poten­tial in the cardiac myocytes is -90 mV (-85 to -95 mV). The cardiac muscle has slower but prolonged action potential than skeletal muscle that lasts for 150 ms in atria and 300 ms in ventricle.

Cardiac myocytes have three types of membrane ion channels that play a crucial role in causing the voltage changes of the action potential. They are (1) fast sodium channels, (2) slow sodium-calcium channels, and (3) potas­sium channels.

During the depolarization phase of the action potential, the membrane potential rapidly reverses to a positive value of about +20 to +30 mV (depending on the myocardial cell) as a result of activation of voltage-gated Na⁺ channels and subsequent rapid entry of the Na⁺ ions into the cells.

The slow channels are slow to open and remain in the open state for a few tenth of a second. The slow channels are activated at a membrane potential of -30 to -40 mV. The action potential spikes when the rapid Na channels are activated, while the action potential plateaus when the slow channels prolong the transit of Ca²⁺ ions into the cell’s interior.

The inflow of Ca²⁺ ions into the cardiac muscle cells decreases K⁺ efflux through voltage-gated K channels. This delays the K⁺ ion permeability to outside, which in turn delays the repolarization process of the action potential in cardiac muscle. In cardiac myocytes, repolarization does not occur immediately after depolarization, but the positivity remains as a plateau near the peak of the spike potential.

This plateau lasts for a few hundred milliseconds and prolongs the contraction of the cardiac muscle as shown in Fig.

6.3.2.1 Action Potential in Pacemaker Cells

The pacemaker cells of the SA node have an inherent prop­erty of generating their own action potentials rhythmically, independent of nerve stimulation, and they depolarize faster than any other part of the heart. The ability of pacemaker cells to self-stimulate is known as automaticity or rhythmicity. Automaticity is due to slow, spontaneous, and progressive depolarization of membrane potential until the threshold potential is reached, which initiates an action potential.

The resting membrane potential in the sinus nodal pace­maker cells (pacemaker potential) is -55 to -60 mV. The cause of this lesser negativity is that the cell membranes of the sinus fibers are naturally leaky to sodium and calcium ions. At this level of -55 mV, fast sodium channels are “inactivated,” i.e., they have become blocked. This is because when the membrane potential remains less negative than about -55 mV for more than a few milliseconds, the fast sodium channels become closed. Therefore, only the slow sodium-calcium channels can open and thereby cause the action potential.

The initial decrease in resting potential is produced by natural inward leakiness of positive Na⁺ ions (higher Na⁺ concentration outside the nodal cells and moderately open Na⁺ channels are the causes for Na⁺ leaking to inside); this slowly brings the membrane potential to -40 mV at which potential the slow Na⁺-Ca²⁺ channels become activated (open); Na⁺-Ca²⁺ ions move inward and depolarize the mem­brane producing an action potential. The Na⁺-Ca²⁺ channels become inactivated within about 100-150 ms after opening, and at the same time, more numbers of K⁺ channels open. Therefore, influx of Na⁺ and Ca²⁺ ions through the Na⁺-Ca²⁺ channels stops, while large quantities of positive K⁺ ions diffuse out of the cell.

Stimulation of vagal fibers to heart hyperpolarizes the membrane potential since the acetylcholine increases out­ward K⁺ conductance producing hyperpolarization of pace­maker cells. The result is a decrease in firing rate from SA node, and the heart rate is decreased. Very strong stimulation of vagus abolishes spontaneous discharge of SA node cells for some time.

Stimulation of sympathetic cardiac nerves makes the membrane potential to decrease rapidly and increases sponta­neous discharge rate, and the heart rate is increased.

6.3.2.2 Specialized Excitatory and Conduction System of Heart

Impulse formation and conduction are carried out by three types of cells: nodal cells, Purkinje cells, and transitional cells.

Nodal cells are seen in sinoauricular node that is responsi­ble for pacemaker impulse generation and in atrioventricular node, which is responsible for conduction delay.

Purkinje cells are larger cells specialized for rapid impulse conduction and are found in bundle of His, bundle branches, and Purkinje network.

Transitional cells connect Purkinje cells and contractile myocardial cells.

These specialized excitatory and conduction fibers show very feeble contractions because of the presence of very few contractile fibers.

In mammals, the sinoatrial node is a small, flattened, ellipsoid strip of specialized cardiac muscle, located at the junction of the right atrium and cranial vena cava. It has an inherent property of generating its own action potential at periodical interval. The ends of the sinus nodal fibers connect directly with surrounding atrial muscle fibers. Action potentials therefore move into these atrial muscle fibers after leaving the SA node.

SA node spreads its impulse through atrial muscular wall, interatrial bundles to atria, and through the anterior, middle, and posterior internodal pathways to AV node (atrioventric­ular node), which lies in the septal walls of the right atrium craniodorsal to tricuspid valve. AV node conducts action potentials to common bundle of His or AV bundle, which then runs into the ventricular septum where it divides into right and left bundle branches that run underneath the septal endocardium. The AV node and AV bundle are the only routes for the conduction of impulse from atria to ventricles. The AV node conducts the action potential very slowly. It takes 50-150 ms for an action potential to pass through the AV node. The nodal delay is contributed by the junctional fibers, which are very small fibers that connect the atrial fibers with nodal fibers. After the AV nodal delay, the impulse travels rapidly down the septum via the right and left branches of the bundle of His, and at the ventricular apex, the bundle branches finally terminate into Purkinje fibers, which are a network of conductive system in the ventricular muscle. The network of fibers in this ventricular conduction systems are specialized for rapid propagation of action potentials. These fibers coordinate and hasten the spread of ventricular excitation to ensure that the ventricles contract as a unit. The action potential is transmitted through the entire Purkinje fiber system within 30 ms. The impulse quickly spreads from the excited cells to the rest of the ventricular muscle cells by means of gap junctions.

6.3.2.3 Propagation of Action Potential

Once initiated in the SA node, an action potential spreads throughout the rest of the heart. The right atrium begins to depolarize about 0.01 s before the left atrium. Purkinje fibers have the highest conduction velocity, while AV nodal fibers have the lowest conduction velocity. AV node delays the conduction velocity of action potentials to the ventricular musculature, which is referred to as nodal delay, and this allows the atrial contractions to occur a short time ahead of the ventricular contraction and thus facilitating the atria to discharge their blood into the ventricles before ventricular systole.

In part, the slow conduction velocity across the AV node is due to the small diameter of nodal myocytes and the complex arrangement of the myocytes, which makes the action potential follow a more tortuous path through the AV node. Additionally, the slow conduction velocity of the AV node is due to the poor expression of Na⁺ channels, poor electrical coupling between the myocytes of the AV node, and lack of high-conductance connexins in the gap junction.

The self-excitation is greatest in the SA node fibers. The normal rate of discharge in SA node is 70-80/min; AV node—40-60/min; and Purkinje fibers—15-40/min. Hence, it is called as cardiac pacemaker. The SA node dominates the normal rate and rhythm of the heart, and hence the SA node normally controls the rate of the heart. In some pathological conditions of the mammalian heart, the excitatory impulses originate outside the SA node and such place is referred to as ectopic foci in which the heart rate will be less than normal. This rhythm is called as ectopic rhythm.

The velocities of conduction of impulse (m/s) of different conducting systems are atrial pathways—1; AV node—0.05; bundle of His—1; Purkinje fibers—4; and ventricular muscles—1.

6.3.2.4 Neural Control of Myocardial Rhythmicity and Impulse Conduction

The heart is supplied with both sympathetic and parasympa­thetic nerves. Stimulation of the sympathetic nerves releases norepinephrine at the sympathetic nerve endings, which increases the permeability of the sinus node fiber membrane to sodium and calcium ions, causing more positive resting potential and also increasing the rate of upward drift of the diastolic membrane potential toward the threshold level for self-excitation, thereby increasing the heart rate. Further­more, increase in permeability to calcium ions increases the contractile strength of the cardiac muscle.

Stimulation of the parasympathetic nerves to the heart (vagus) causes acetylcholine to be released at the vagal endings. This hormone decreases the rate of rhythm of the sinus node and also decreases the excitability of the AV junctional fibers between the atrial musculature and the AV node by causing hyperpolarization through increasing the permeability of potassium ions into the cells of SA and AV nodes, thereby slowing the transmission of cardiac impulse into the ventricles. Weak to mild vagal stimulation slows the heart rate to one half normal. Strong stimulation of the vagi can completely stop the rhythmical excitation by the sinus node or completely block transmission of the cardiac impulse from the atria into the ventricles through the AV node, but then, ventricular escape occurs wherein the ventricular septal region of the AV bundle establishes its own rhythm and stimulates ventricular contraction at a rate of 15-40 beats per minute.

6.3.3 Electrocardiogram

The electrocardiogram (ECG) is the most widely used nonin- vasive clinical tool for diagnosing electrical dysfunctions of the heart, wherein two or more metal electrodes are applied to the skin surface, and the voltages recorded by the electrodes are displayed on a video screen or drawn on a paper strip.

6.3.3.1 Principles of ECG Recording

The depolarization and repolarization of the cardiac muscles generate electrical currents, which spread into the tissues around the heart and are conducted through the body fluids. A small part of this electrical activity reaches the body surface, where it can be detected using recording electrodes.

Electrocardiography provides a record of how the voltage between two points on the body surface changes with time as a result of the electrical events during the cardiac cycle. At any instant of the cardiac cycle, the electrocardiogram gives the net electrical field that is the summation of many weak electrical fields being produced by voltage changes occurring on individual cardiac cells at that instant. The ECG can be recorded by either using an active or exploring electrode connected to an indifferent electrode at zero potential (unipo­lar recording) or using two active electrodes (bipolar recording).

6.3.3.2 Lead Systems

ECG is recorded by placing a series of electrodes on the body surface. These electrodes, called ECG leads, are connected to the ECG machine at one end and are fixed on the left fore­limb, right forelimb, and left hind limb at the other end. Electrodes on these limbs are usually envisioned as forming a triangle around the heart. Heart is in the center of an imaginary equilateral triangle (Einthoven triangle) drawn by connecting the roots of these three limbs. ECG is usually recorded in 12 leads, which are generally classified into three categories:

1. Bipolar leads

2. Unipolar leads

3. Chest leads

6.3.3.2.1 Bipolar Limb Leads (Standard Limb Leads) Herein, two limbs are connected to the electrode and both the electrodes are active recording electrodes, i.e., one electrode is positive and the other one is negative. The right hind limb is connected to the earth.

A triangle can be formed by placing the three electrodes on right forelimb, left forelimb, and left hind limb with the heart at the center.

If electrical potential of any two of the three bipolar leads is known at a given instant, the third one can be calculated,

i. e., the sum of voltage in lead I and III equals the voltage in lead II (Einthoven's law).

Standard limb leads are of three types:

1. Limb lead I: The voltage in the left forelimb compared with the right forelimb is called lead I. Right forelimb is connected to the negative terminal of the instrument, and the left forelimb is connected to the positive terminal.

2. Limb lead II: The voltage measured in the left hind limb is compared with the right forelimb. Right forelimb is connected to the negative terminal of the instrument, and the left hind limb is connected to the positive terminal.

3. Limb lead III: Lead III is obtained by connecting left hind limb and left forelimb. Left hind limb is connected to the negative terminal of the instrument, and left forelimb is connected to the positive terminal.

6.3.3.2.2 Unipolar Leads

In unipolar lead system, wires from two limb electrodes of the bipolar lead system are connected together and the mean electrical potential of these two leads is measured by the electrode called indifferent electrode, which is attached to the negative terminal of the ECG. Recording is taken, wherein one electrode is an active electrode and the other one is an indifferent electrode. Active electrode is positive or exploring and is placed on the third limb, and indifferent electrode serves as a negative electrode. In unipolar leads, mean electrical potential difference sensed by the indifferent and reference electrodes is measured. This is able to detect greater potential difference.

Unipolar limb leads (augmented voltage leads) are of three types:

Unipolar limb leads are also called augmented limb leads (as compared to the regular leads, the augmentation of deflections occurs). Active electrode is connected to one of the limbs, and indifferent electrode is obtained by connecting the other two limbs through a resistance.

1. aVR lead: Lead aVR measures the voltage from the right forelimb electrode compared with the average voltage from the other two limb electrodes. Active electrode is from right forelimb, whereas indifferent electrode is obtained by connecting left forelimb and left hind limb.

2. aVL lead: Active electrode is from left forelimb, and indifferent electrode is obtained by connecting right fore­limb and left hindlimb.

3. aVF lead: Here, the voltage measured from the left fore­limb (active) electrode is compared with the average volt­age from the other two limb (indifferent) electrodes.

Leads I, II, and III are used routinely in veterinary electro­cardiography. Recordings from the augmented unipolar limb leads (aVL, aVR, and aVF) are also often included.

6.3.3.2.3 Chest Leads

The precordial (chest) leads are used more often in human medicine than in veterinary medicine. These special additional leads are sometimes recorded by placing ECG electrodes at standardized sites on the thorax. They are helpful in the evalu­ation of very specific cardiac electrical dysfunctions.

6.3.3.3 ECG Waves

The ECG recording consists of waves, complexes, intervals, and segments. Deflections of normal ECG are known as waves, namely P, Q, R, S, and T.

P wave indicates the sum of all the electrical potentials produced during the depolarization of both atria and the spreading of the electrical activity from SA node throughout the atrial musculature. It starts the atrial contraction and somewhat comes before atrial systole. Due to the temporal lag between electrical and mechanical events, there is only a very brief delay between the P wave and atrial systole.

The QRS complex indicates ventricular depolarization wave initiating ventricular systole. QRS wave precedes isovolumetric contraction. It consists of three components.

Q wave is the first negative (downward) deflection of ECG; it indicates the spreading of electrical impulses from the left septal surface toward the right and from there toward the left.

R wave, a positive (upward) deflection, represents the spreading of impulses from the subendocardial termination of Purkinje system toward the epicardial surface of both ventricles via muscle fiber to muscle fiber conduction.

S wave, a negative deflection, indicates the conduction of impulses on the muscle fibers at the base of the heart and their activation.

T wave, the positive (upward) deflection, indicates the beginning of ventricular repolarization (relaxation).

ECG has no separate deflection or wave for atrial relaxa­tion, which is due to the fusion of this deflection with QRS complex.

6.3.3.4 ECG Intervals

P-Q interval: It is the time duration between the beginning of the P wave and the beginning of the QRS wave. It indicates the time the excitation wave travels from SA node to Purkinje system and includes short AV nodal delay after the atrial contraction to permit complete ven­tricular filling. P-R interval indicates atrioventricular con­duction time. Normally, P-R interval is 0.1 s.

Q-T interval: It is the duration from the beginning of Q wave to the end of T wave, which indicates the duration of time from initiation of ventricular depolarization to completion of repolarization or ventricular contraction.

S-T interval: Duration from the beginning of S wave to the beginning of T wave during which the ventricles remain depolarized.

From the end of P wave to the beginning of Q wave and from the end of S wave to the beginning of T wave, the ECG does not exhibit any waves; that is, the electrical potential of the cardiac musculature does not undergo any alteration (remains at isoelectric potential).

The time between successive P waves is P-P interval, and it corresponds to the time between atrial contractions.

P-R interval can be used to calculate the number of atrial contractions per minute. Similarly, R-R interval can be used to calculate the ventricular rate.

6.3.3.5 Vector Analysis and Mean Electrical Axis

6.3.3.5.1 Cardiac Vector Analysis

The standard limb leads record the potential difference between two points on the body surface, and the deflection produced in each lead at any given instant indicates the magnitude and direction of passage of cardiac potential.

Cardiac vector (cardiac axis) is the direction at which electrical potential generated in the heart travels at an instant. It indicates the magnitude and direction of the cardiac poten­tial at any given instant. The vector for a given moment can be calculated by using any two standard limb leads. If the net potential of the QRS complex in two leads is measured, the mean vector for the ventricular depolarization can be calcu­lated. The direction of this vector is called electrical axis of the heart.

6.3.3.5.2 Calculation of Mean Electrical Axis

An equilateral triangle is drawn, and the positions of electrodes with their polarity of each point of the standard leads are marked. In each lead, distances equal to the height of R wave minus the height of the largest negative wave in the QRS complex are measured and marked in the positive direction from the midpoint, on the side of the triangle representing that lead. All the three perpendiculars are extended, which intersect at a point within the triangle. An arrow called mean electrical axis of the heart or mean QRS vector is drawn from the center of electrical activity to the point of intersection of perpendiculars. The length of the arrow indicates the magnitude, and the arrowhead indicates the direction of the electrical activity. The normal direction of electrical axis is -30° to +110° (on an average of 70°). If the calculated axis falls to left of -30° or right of + 110°, left- or right-axis deviation is said to be present. Right-axis deviation indicates right ventricular hypertrophy, and left-axis devia­tion is due to left ventricular hypertrophy. Mean electrical axis of the dog’s heart lies between +40° and +100° and in cats it is 0° to +160°.

6.3.3.6 Significance of ECG

It is a noninvasive method that aids to evaluate cardiac function; diagnose ventricular hypertrophy; evaluate conduction system blocks, myocardial infarction, drug effects, etc.; assess heart rate and rhythm; evaluate myocardial electrical conduction; and assess any myocardial abnormality.

Ventricular hypertrophy increases R amplitude (high voltages) of the QRS complex in leads II and III:

Right ventricular hypertrophy—the polarity of the R wave of QRS complex is negative instead of the normal positive in lead I.

Right or left ventricular hypertrophy—slightly prolonged QRS with high voltage.

Hypertrophy of left ventricle—abnormally high amplitude of the R wave in lead I.

Enlargement of the atria—wider P wave.

Bundle branch block—axis deviation along with prolonged QRS duration.

Cardiac tamponade, accumulation of fluid in the pericardium—low voltage of ECG waves.

Sinus tachycardia (tachycardia is increase in heart rate; sinus indicates SA node activity)—the ECG recording shows normal waves, i.e., P wave followed by QRS complex and T wave but with increased frequency of waves per minute.

Sinus bradycardia (heart rate is reduced below the normal)— the ECG recording shows normal waves, i.e., P wave followed by QRS complex and T wave but with decreased frequency of waves per minute.

First-degree AV block—the PR interval is abnormally long suggestive of long delay in the propagation of action potentials through AV node and AV bundle.

Second-degree AV block—some P waves are followed by QRS and T waves but some P waves without QRS and T waves, i.e., successive P waves occur with missed ventric­ular beats. Some atrial impulses fail to be conducted to ventricles.

Third-degree AV block—if QRS wave is not preceded by P wave and the frequency of P and QRS waves is different, i.e., asynchrony of P and QRS waves is observed. Itoccurs when conduction from atria to ventricles is completely interrupted.

6.4