Pacemaker Electronics

In electronic systems, circuits capable of generating automatic impulses is often required. They serve important roles as clock circuits in computers, electronic clocks, timers and many others. Learning the way they act, may shed some intuition in the working of our own physiological signal generators; be they in the pacemaker node of the heart or the cells of Cajal in the intestine or the pulsatile circuit in the hypothalamus!

The animated picture/schematic on the left portrays an oscillator circuit, called the L C tank circuit (L= inductor, C= capacitor). The coil represents the inductor, while the two parallel horizontal lines represent the capacitor. No voltage source is shown (for simplicity) as such but let us assume that the capacitor is already starting with an initial voltage.

Lets assume that the capacitor plates are fully charged from the beginning (and there's no other activity anywhere in the circuit). The charged plates of the condenser will discharge through the inductor coil. Like all other electrical conductors these coils are resistive, obeying the Ohm's Law. But in addition to the resistive load, they resist the passage of electricity in another way called 'inductance'. As electrons move through these coils, a magnetic flux (change of field) is created; this magnetic flux, in turn, create electricity that oppose the primary current (didn't we know that electricity and magnetism were related?). Once the flow of electrons have ceased, the magnetic field collapses. This collapsing (=changing) magnetic field then induces a voltage of opposite polarity in the condenser. This voltage is again discharged through the coil, which opposes it as described, produces a back EMF as per Lenz's law and charges the capacitor back. This cycle goes on repeatedly, producing a oscillating waveform.

Electronic circuits also employ RC circuits (resistor capacitor), Crystal controlled oscillators, dedicated waveform generator ICs (such as the ubiquitous 555 type, ICL 8038, XR 2206) and various others. Nowadays quartz crystals are being increasingly used for reasons of accuracy, among others. They also operate in a similar way, as an equivalent circuit of a crystal is shown on the left will demonstrate. These crystals also bear an uncanny similarity with muscular elements in our bodies: resistive and elastic elements.

Our pacemakers too work in an analogous fashion. Though Mr Henry (inductors are measured in henry/ microhenry etc) is probably not there; there is depolarization (upstroke) caused by leaking calcium ions, followed by repolarization (downstroke) caused by closing of calcium currents and opening of potassium channels leading to efflux of positive charges from the cells' interior. Electronic waveform generators are integral part of artificial pacemaker devices. They may even help us understand how in physiology autorhythmicity is produced. Our knowledge about biological mechanisms are far from complete and still evolving.

Last modified: never
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Treating Arrhythmias: Quelling The Riot

To make the cardiac contractions hemodynamically effective and to avoid the dangerous consequences of arrhythmias, treatment is often necessary. Pharmacotherapy, electrical therapy using defibrillator, pacemaker implantation, radio-frequency ablation and even surgery are some methods that are available.

Bradyarrhythmias arising due to AV block (conduction disturbance) may be treated with vagolytics (parasympatholytics) like atropine, or sympathomimetics like isoproterenol (isoprenaline), given intravenously. These medications increase the heart rate. The heart is innervated by the vagus nerve, which secretes acetyl choline when stimulated. This chemical combines with a receptor molecule, called muscarinic receptor, type M2, on the cell membrane of the heart muscles. After combining, they give instructions to some other substances in the cell membranes called G proteins, to open the potassium channels. Potassium being more in the interior of the cell, leaks to the outside, along the gradient. This efflux of K+ ions make the cell more negative (hyper-polarized) and thus less excitable, lowering the speed of conduction. Atropine, an antimuscarinic drug, does not let this happen. Potassium channels are NOT opened and the cells are as more excitable. Impulse can pass easily now. Sympathetic nervous stimulation, through beta receptor stimulation, or drugs like isoprenaline also increase the speed of conduction.

A better way of tackling bradyarrhythmias is through the implantation of a pacemaker, an artificial one. These devices have a stimulating electrode which passes through some vein on the surface of the body straight to the right atrial appendage or the apex of the right ventricle. These pacemakers have a coding nomenclature (like the color coding of resistors or capacitors) that describe them. For example, in the usual VVIR type, the first letter 'V' indicates that it is the ventricle that is paced (i.e. stimulated); the second 'V' means that the pacemaker senses the ventricles to determine its action (described later); 'I' means that the action will be inhibitory (i.e. if it senses that an impulse is normally there in the ventricle, it will inhibit the next impulse from the artificial pacemaker); whereas R means that it is rate controlled. This protocol is much like the color coding of resistors in electronics. Pacemakers are also useful in the treatment of paroxysmal tachycardias (the implanted pacemaker depolarizes ahead of the ectopic signal and make aberrant conduction difficult through the now refractory tissue.)

Pharmacotherapy, using antiarrhythmics, is rather disappointing. In the CAST study (cardiac arrhythmia suppression trial), it was shown that patients treated with one of the drugs (moricizine or flecainide or encainide) had actually more mortality than the control group. In fact, antiarrhythmics are themselves arrythmogenic (proarrhythmic). However, amiodarone, beta blockers, adenosine and some other drugs do seem to confer some benefit.

Implantable cardioverter defibrillators (ICD) are very useful. They sense arrhythmias and send DC shock upto 40 W.s (Watt seconds), to tame the 'revolting rebels'. This 'recognize and treat' methodology based tool (picture shown) is very useful. Another useful approach is by using catheters with a probe electrode at their tips. They can virtually sniff out the abnormal focus by mapping (electrophysiology study or EPS), which are later burned, using radio frequency currents (RF ablation). Radio frequency ablation is very helpful in burning out the aberrant bundle of Kent in WPW syndrome, in atrial flutter, AV nodal reentrant tachycardias and others.

Role of surgery is very minimal. It is invoked only when other measures fail and in some recalcitrant cases. While the above information is important, one must never forget the immense significance of cardiopulmonary resuscitation (CPR) in this regard. This intelligent step consisting of pressing the sternum (breastbone) with the heel of the hand and giving artificial respiration through the mouth simultaneously, is life saving. Here in this case, the first part, i.e. pressing the sternum is particularly important as it will pump the heart from outside and result in a cardiac massage. In a suspected event of cardiac arrest where the heart has stopped (i.e. no effective cardiac output), do a CPR first, save a life!

Last modified: Mar20, 2009
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The Circus of Arrhythmias

Everything goes well as long as the heart 'plays its own symphony' and 'orchestrates this opera with the elan of a master conductor'. Problems occur when there is a fault in the generation or conduction of this rhythm or both. Arrhythmias (aka dysrhythmia), an emergency, sometimes fatal, may occur.

Consider for example, that if the SA Node STOPS producing its impulse (sinus arrest), will we die then?
There are other parts in the heart which are capable of generating impulses. For example, in physiology, you can find two such in the His bundle itself; one proximally (near the SA Node) and the other distally (further away from the SA Node) in the His bundle. They produce impulses, under such circumstances. So, when the pacemaker of the heart ( SA Node) fails, we don't die as these centres take over. If you go down the hierarchy of impulse generating pacemakers from the SA Node, the pace of discharging frequency decreases. Proximal His bundle has a pace of about 45 beats per minute while distally in the His bundle the frequency is around 35. This really is a remarkable safety feature of the heart (another safety feature is that the heart muscle can not be tetanised).

Thus, in sinus arrest, the lower parts in the conduction system will start functioning (as the normal pacemaker fails), albeit at a reduced rate. When the SA node is producing impulses but these impulses are NOT being CONDUCTED to the atria (Sino-atrial exit block), a similar situation will result. The heart continues beating, but at a lower rate.

Broadly speaking, arrhythmias has been divided into two types: bradyarrhythmias and tachyarrhythmias. When the heart rate is less than 60 per minute, it is known as bradyarrhythmia (brady meaning slow) while in tachyarrhythmias (tachy=rapid), heart rate is above 100 per minute. Suppose on its conduction to the ventricles, the impulse faces a block, and no impulse is reaching the ventricles: a condition known as complete heart block or third degree heart block will result. The second-in- hierarchical command will take over then i.e. the centers in the His bundle will now assume function.

Since these centers have lower frequency of operation, they are dominated over by their high frequency cousins, 'the SA node'. Given their low discharge rates they are 'overdriven' by the SA node pacemakers. Thus when the SA node blacks out or there is a conduction disturbance, these lower centers don't resume spot on (because it takes time for them to 'recover' from the 'overdrive'). The ventricles beat at a low rate independent of the atria, a phenomenon called the Idioventricular rhythm, starts. It takes time for the ventricles to resume function. The brain passes out after about 5-7 seconds as it can not tolerate the hypoxia. the silence of the ventricles (No impulse means no contraction) and Stokes-Adams syndrome consisting of dizziness, vertigo (feeling of the head spinning) and syncope (fainting) may occur. The above are examples of bradyarrhythmias.

Tachyarrhythmias occur when there is enhanced automaticity ( exogenous or endogenous catecholamines, digitalis glycosides, hyperkalemia make the cardiac tissue more excitable), triggered activity (changed electrical property of the heart, triggered by factors such as early after depolarizations or EAD and delayed after depolarizations or DAD) and re-entry or circus movement. Normally, the impulse propagates unidirectionally. If a unidirectional block occurs along the conduction system, it may give rise to re-entrant arrhythmias. Also, in WPW syndrome (or Wolff Parkinson White syndrome) an abnormal bypass tract, called the bundle of Kent, connects the right ventricle with the atria. The speed of conduction through this aberrant bundle is more rapid than through the AV bundle. The impulse that goes forward (antegrade) through this bundle comes back to re-excite the atria (retrograde) through the normal AV bundle, establishing a re-entry circuit. The heart beats fast. In conditions such as atrial flutter (picture on the left), the impulse goes around and around, at rates as high as 200-350 per minute. In atrial fibrillation, multiple ectopic foci discharges, and that too in a haphazard manner. The rate of discharge is between 300-500 per minute. But not all these impulses will find their way through to the ventricles, since the AV node can not carry impulses more than 230 per minute. The diseased muscles of the ventricles, like their atrial counterparts, acquire the ability of self discharging giving rise to conditions as ventricular tachycardia and ventricular fibrillation, a very fatal outcome of myocardial infarction (MI), where the ventricles feel like 'bag of worms'.

Not all arrhythmias are pathological though. All sinus tachycardia, sinus bradycardia need not be considered a medical problem, since they may be found in cases of anxiety ( tachycardia) and in athletes (bradycardia) respectively. However, sick sinus syndrome, which presents with bradycardia is pathological.
Sinus arrhythmia refers to increase in heart rate with respiration. This is absolutely physiological. In fact, in diabetics sinus arrhythmia is absent. The human body is really puzzling!

You might be tempted to ask how does arrhythmia harm us anyway. Tachyarrhythmias make the heart beat so fast that it hardly has enough time to fill itself with enough blood for the system. The cardiac output fails. There may be clot formation (thrombosis) in the cardiac chambers, specially atria, and concomitant embolism. Bradyarrhythmias on the other hand, deprive the brain of its vital dose of oxygen. In either case, a sensation of an irregular beat or palpitation, may make the patient anxious and apprehensive.

Impulse Propagation In The Heart

In the previous article, we discussed how the pacemaker of our heart, the SA node, was generating the rhythmic impulses. For the impulse to have any effect, it has to be travel to various parts of the heart, which will then contract as a result.

After its generation, the impulse goes to the AtrioVentricular Node. It supplies both the atria, while on their way to the AV Node. The sojourn of impulse, between the SA and the AV node, is via the internodal pathway.

There is a delay of about 0.09 second in the AV node itself. The anatomy and physiology of the AV node is responsible for it. It is said that the nodal cells have fewer gap junctions among themselves, making ionic flow highly resistive. Nevertheless, this delay serves a useful purpose. As seen in the animation, the atria contract when they are stimulated and fill the ventricles with blood. Were it not for the delay, the ventricles would fire near simultaneously, without their quota of blood from the atria, and thus producing hemodynamically ineffective cardiac output. It gives the ventricle vital time to fill. Since the junction between the atria and ventricles is electrically non-conducting (due to the presence of a fibrous partition between the two chambers of the heart. The conduction pathway is like electrical cabling between 2 floors of a building), the impulse must find a route to pass through. It has only one way, in normal physiology, through which it can travel: through the penetrating portion of the AV bundle.

So, from here onwards, the impulse is carried via the AV bundle, down the interventricular septum. The AV bundle then bifurcates into right and left bundle branches, which traverse along right and left ventricle respectively. From there, Purkinje fibres arise which ultimately supplies the ventricular muscles.

As the impulse travels down the septum, it reaches the apex of the heart, and supplies the ventricular muscles. Next, the impulse travels along the ventricular musculature upwards towards the atrioventricular septum, the top portion of the inter ventricular septum and the posterobasal portion of the heart. These are the areas to be depolarized last. While doing this part of the journey, the impulse also spreads from the endocardium to the epicardium; that is they travel from the inside of the heart to the outside. All these can be seen in the adjoining picture/animation. This animation also portrays how the ECG would be like, with the spread of the wavefront. The state of the heart valves can also be seen during systole and diastole, i.e. during the contraction/relaxation of the cardiac chambers.

The conduction system comprising of internodal tracts, AV bundle, His-Purkinje fibers are all specialized muscle cells, that carry electricity at high speeds. Also, all these depolarizations are followed by repolarizations, making the cells ready for the next impulse. The action potential characteristic of cardiac muscles are different from that of the pacemaker cells.

In some idiopathic degenerative diseases, the fibrous skeleton of the heart may be calcified and sclerosed, as in Lev's disease, or there may be sclerodegenerative changes within the conducting system sparing the myocardium or the fibrous skeleton, as in Lenegre's disease. Here the 'electric cable connecting the first and the second floor of the heart' (i.e. the piercing AV bundle); is naturally snapped (due to the interposition of non conductive sclerosed material), leading to AV block and bradycardia of varying degree.

PS: Click on the animation if it doesn't animate on its own.

Last modified: Mar 20, 2009
Reference: hyper-links, unless specifically mentioned

Generation Of Cardiac Rhythm

The heart is vital to our bodies, since it pumps blood into various parts of our bodies, that provide us oxygen, nutrients and takes away the metabolites for disposal. For this, the heart has to contract in order to generate enough force for the ventricles (atria too) to have a standard ejection fraction. Not only does it contract, it also generates the impulses necessary for its contraction, a property called automaticity, by which it generates its own rhythm.

The cells in our bodies are bathed in a sea of fluid. This fluid, called the extracellular fluid or ECF, as it is located outside the cells. The ECF is rich in sodium ions (Na+), while their concentration inside the cells are much less. Conversely, the concentration of potassium ions (K+) is more inside than outside. It is due to this difference in concentration of ions on either side of the cell membrane, a transmembrane voltage is produced. These ions being polar in nature and water soluble, can not penetrate the lipid cell membrane. But they can gain entry, through specialized pores called ion channels.

The sodium ion channels, channels through which sodium ions pass, has 2 gates: an activation gate and an inactivation gate. What controls these gates is not known for sure, but it could either be an energy barrier controlling its entry or a flexible peptide chain-like stuff that alters the conformation of the gates to restrict the ion's access. Extracellular calcium ions also restrict sodium ions to go through and thus has a stabilizing effect. These gates are called voltage controlled gates, since the opening or closure of the gates are controlled by transmembrane voltage. These gates are inactivated at voltages above -55mV (i.e. say -40 mV) and no sodium ion can pass. Below -70 mV , the gates are open, allowing free flow of Na+ along the electrochemical gradient, from the exterior to the interior of the cell.

There are areas of heart other than the sinus node which have intrinsic automaticity i.e. they are capable of generating their own rhythms, such as the Purkinje fibers. But the SA Node (sinoatrial node) is the normal pace-maker, since it fires at the highest rate. In the nodal tissue, where the cell voltage hovers around -60 to -55 mV (millivolt), the sodium ion channels are inactivated at this voltage. Since, the resting membrane potential (RMP) of the pacemaker lies in a region where the sodium channels are inactivated, the firing of the SA Node depends on other ions, particularly calcium ions (Ca++). These nodal pacemaker cells (possibly P cells, containing little organelles) are inherently 'leaky' to calcium ions. So, Ca++ enters these cells making the cells' interiors less negative, (Ca++ is a cation bearing 2 positive charges. A cation is a positively charged ion, so called because it is attracted towards the cathode). Once the cell gains enough positive charge, to become a little more positive, about -40 mV, as shown in the figure (prepotential), there is a sudden spurt of calcium influx (impulse). T type (transient) calcium channels are responsible for the prepotential while L (long lasting) type calcium channels are responsible for the impulse. In addition to the influx of calcium ions from the ECF, calcium is also liberated locally from the sarcoplasmic reticulum of the nodal cells, known as the 'calcium spark'. So, the cell is now fully depolarized, as shown. But soon calcium channels close and influx stops. Potassium channels open. Since the concentration of K+ is more inside, K+ leaves the cell making the interior more negative. The efflux of K+ and stopping of further influx of Ca++ repolarizes the cell, making it ready for another cycle. Ca++ leaks again and the cycle repeats.

The colored animation on the top left shows the spread of cardiac impulse, from the SA Node. Click on the animation if it doesn't animate on its own.

Last modified: Mar20 2009
Reference: Basic and Clinical Pharmacology, Bertram G Katzung, 9th ed, page 220