Cardiac Arrhythmias: Difference between revisions

 

 

= General Introduction =

A basic knowledge of the physiological cardiac action potential and cardiac conduction system facilitates understanding of cardiac arrhythmias. The effects and side-effects of anti-arrhythmic drugs are depended on the influence on ion channels involved in the generation and/or perpetuation of the cardiac action potential.

The cardiac action potential is a result of ions flowing through different ion channels. Ion channels are passages for ions (mainly Na⁺, K⁺, Ca²⁺ and Cl^-) that facilitate movement through the cell membrane. Changes in the structure of these channels can open, inactivate or close these channels and thereby control the flow of ions into and out of the myocytes. Due to differences in presence of the type and structure of ion channels, the various parts of the cardiac conduction system have slightly different action potential characteristics. Ion channels are mostly a passive passageway, where movement of ions is caused by the electrochemical gradient. In addition to these passive ion channels a few active trigger-dependent channels exist that open or close in response to certain stimuli (for instance acetylcholine or ATP). These changes in the membrane potential produce and action potential which lasts only a few hundreds of milliseconds. Disorders in single channels can lead to arrhythmias, as seen in the section [[Primary_Arrhythmias]]. The action potential is propagated throughout the myocardium by the depolarization of the immediate environment of the cells and through intracellular coupling with gap-junctions.  

In summary during the depolarization, sodium ions (Na⁺) stream into the cell followed by a influx of calcium (Ca²⁺) ions (both from the inside (sarcoplasmatic reticulum) and outside of the cell). These Ca²⁺ ions cause the actual muscular contraction. Shortly thereafter potassium (K⁺) ions flow out of the cell (=efflux), causing repolarization. During repolarization the ion concentrations return to their resting concentrations, due to the passive efflux of K⁺ and active exchange of Na⁺ with Ca²⁺ (Figure 1). In detail the (ventricular) action potential can be divided in five phases:  

Rapid depolarization is started once the membrane potential reaches a certain threshold (about -70 to -60 mV), independent of the size of the depolarizing stimulus. This produces a rapid influx of Na⁺ and a rapid upstroke of the action potential. At higher potentials (-40 to -30) Ca²⁺ influx participates in the upstroke. In the sinus node and AV node a slower upstroke can be observed (Figure 2). This is because the upstroke in these cells is mainly mediated by the slower acting Ca²⁺ ion channels. The slower activation produces a slower upstroke.

Immediately following rapid depolarization, the inactivation of the Na⁺ channel (I_Na) and subsequent activation of the outward K⁺ channel (I_to) and the Na⁺/Ca²⁺ exchanger (NCX) produces a early rapid repolarization. Due to the limited role of the Na⁺ channel in the upstroke of sinus node and AV node cells and the subsequent slower depolarization, this rapid repolarisation is not visible in their action potentials.

The plateau phase represents an equal influx and efflux of ions in or out of the cell producing a stable membrane potential. This plateau phase is predominantly observed in the ventricular action potential. The inward movement of Ca²⁺ through the open L-type Ca²⁺ channels (I_Ca-L) and the exchange of Na⁺ for internal Ca²⁺ by the Na⁺/Ca²⁺ exchanger (NCX) are responsible for the influx of ions during the pleateau phase. The efflux of ions is the result of outward current carried by K⁺ (I_Kur and _Ks) and Cl^- ions.

Depending on cell type the resting membrane potential is between -50 to -95 mV, sinus node and AV nodal cells have a higher resting membrane potential (-50 to -60 mV and -60 to -70 respectively) in comparison with atrial and ventricular cardiomyocytes (-80 to -90 mV). The resting membrane potential is mainly caused by differences in the the K⁺ outside the cell and the K⁺ inside the cell. Sinus node cells and AV nodal cells (and to a lesser degree Purkinje fibers cells) have a special voltage dependent channel I_f, the funny current. Furthermore they lack I_K1, a K⁺ ion channel that maintains the resting membrane potential in atrial and ventricular tissue. This channel causes a slow depolarization in diastole, called the phase 4 diastolic depolarization, which results in normal automaticity. Sinus node discharges are regulated by the autonomous nerve system and due to the high firing frequency the sinus node dominates other potential pacemaker sites.

The cardiac conduction system (figure 2) is the highway though which the electric activity of the heart spreads from the atria to the ventricles. The characteristics of the different parts of the conduction system are a result of the different characteristics of the individual myocytes. On a larger level, function is controlled predominantly by the autonomic nervous system (both vagal and sympathetic nerve system). Especially the sinus node and atrioventricular node are responsive to the autonomic nerve system. The ganglionic plexi, a conglomeration of both vagal and sympathetic nerves, form the intrinsic cardiac nerve system and innervate through a network of nerve fibers the atria and ventricles. The vagal and sympathetic nerve system are both continually active in the heart, but vagal activity dominates the tonic background stimulation of the autonomic nerve system. Moreover the heart is more susceptible to vagal stimulation. Vagal stimulation provokes a rapid response and the effect dissipates swiftly in contrast to sympathetic stimulation which has a slow onset and offset. Vagal stimulation results in a reduction in sinus node activation frequency and prolongs AV nodal conduction. These effects can occur simultaneously or independent of each other.  Sympathetic stimulation exerts reverse effects, accelerating the sinus node firing frequency and improving AV nodal conduction. The autonomic nerve system has a small effect on cardiomyocytes. Vagal stimulation tends to prolong the refractory period and decrease the myocardial contractility. Sympathetic stimulation has the opposite effect on the cardiac tissue. Whereas the physiological modulation of cardiac conduction is vital to adaptation of the heart to rest and exercise the autonomic nervous system can attribute to the pathologic substrate in a diseased myocardium.

The sinus node is an densely innervated area located in the right atrium which is supplied by the right (55%-60%) or circumflex (40%-45%) coronary artery. It is a small structure of 10-20mm long and 2-3mm wide and contains a diversity of cells. These include pacemaker cells which are discharged synchronously due to mutual entrainment. This results in an activation wave front activating the rest of the atrium.

From the bundle of His the right bundle branch continues to the right ventricular apex. The left bundle branch splits of and divides in two or more fascicular branches. Commonly the left bundle branch consist of an anterior fascicle, which activates the anterosuperior portion of the left ventricle. and the thicker and more protected posterior fascicle which activates the inferoposterior part of the left ventricle.

===Venticle===

The ventricle is activated through the dense network of Purkinje fibers originating from the bundle branches. They penetrate the myocardium, but predominantly the endocardium, and are the starting point of the ventricular activation. The left ventricular areas first excited are the anterior and posterior paraseptal wall and the central left surface of the interventricular septum. The last part of the left ventricle to be activated is the posterobasal area. Septal activation starts in the middle third of the left side of the interventricular septum, and at the lower third at the junction of the septum and posterior wall. Activation of the right ventricle starts near the anterior papillary muscle 5 to 10 msec after onset of the left ventricle.<cite>Durrer</cite>

Structural abnormalities or electric changes in the cardiomyocytes can impede impulse formation or change cardiac propagation, therefore facilitating arrhythmias. Arrhythmogenic mechanisms can arise in single cells (automaticity, triggered activity), but other mechanisms require multiple cells for arrhythmica induction (re-entry).  We briefly discuss the pathofysiological mechanisms of the main causes of arrhythmia.

The mechanism of abnormal automaticity is similar to the normal automaticity of sinus node cells. Abnormal automaticity can be caused by changes in the cell ion channel characteristics due to drugs (digoxine) or changes in the electrotonic environment (myocardial infarction). Abnormal automaticity can result from an increase of normal automaticity in non-sinus node cells or a truly abnormal automaticity in cells that don't exhibit a phase 4 diastolic depolarization.

Triggered activity is activity of a cell triggered by a preceding activation. Due to early or delayed afterdepolarizations the membrane potential depolarizes and, when reaching a threshold potential, activates the cell. These afterdepolarizations are depolarizations of the membrane potential initiated by the preceding action potential. Depending on the phase of the action potential in which they arise, they are defined as early or late afterdepolarizations (figure 3).  

* A disturbance of the balance in influx and efflux of ions during the plateau phase (phase 2 or 3) of the action potential is responsible for the early afterdepolarizations. Multiple ion currents can be involved in the formation of early after depolarizations depending on the triggering mechanism. Early afterdepolarizations develop in cells with an increased duration of the repolarization phase of the action potential, as the plateau phase is prolonged.  

Conduction block or conduction delay is a frequent cause of bradyarrhythmias, however tachyarrhythmias can also result from conduction block when this block produces a reentrant circuit. Conduction block can develop in different (physiological) conditions. It is important to assess the cause of conduction block as explained in the section of [[bradycardia]], for it is important in the treatment of the conduction delay or block.

===Reentry===

Reentry or circus movement can arise when an area is slowly conducting thereby still propagating the activation while the rest of the heart depolarizes. When the surrounding myocardium has recovered from this refractory state, and can be stimulated, the impulse in the slow conducting zone can reactivate the heart when it exits the area of slow conduction. This process can repeat itself and thus form the basis of a reentry tachycardia. These areas of slow conduction can be anatomical or functional or a combination of both. Examples of reentry tachycardias are atrial flutter, AVNRT and ventricular tachycardias originating from an infarct zone.<Cite>deBakker</Cite>