Repolarization, cardiac cycle

The Cardiac Cycle. The heart (Eig. lb) performs its function as a pump as a result of a rhythmical spread of a wave of excitation (depolarization) that excites the atrial and ventricular muscle masses to contract sequentially. Maximum pump efficiency occurs when the atrial or ventricular muscle masses contract synchronously (see Eig. 1). The wave of excitation begins with the generation of electrical impulses within the SA node and spreads through the atria. The SA node is referred to as the pacemaker of the heart and exhibits automaticity, ie, it depolarizes and repolarizes spontaneously. The wave then excites sequentially the AV node the bundle of His, ie, the penetrating portion of the AV node the bundle branches, ie, the branching portions of the AV node the terminal Purkinje fibers and finally the ventricular myocardium. After the wave of excitation depolarizes these various stmetures of the heart, repolarization occurs so that each of the stmetures is ready for the next wave of excitation. Until repolarization occurs the stmetures are said to be refractory to excitation. During repolarization of the atria and ventricles, the muscles relax, allowing the chambers of the heart to fill with blood that is to be expelled with the next wave of excitation and resultant contraction. This process repeats itself 60—100 times or beats per minute... 

The QT interval is a dynamic physiological variable depending on multiple factors such as cardiac cycle length (heart rate), autonomic nervous system activity, age, gender, plasma electrolyte concentrations, genetic variations in ion channels involved in cardiac repolarization. In addition, circadian and seasonal variations of the QT interval have been described [93]. 

The ECG consists of the P-wave, the QRS complex, and the T-wave. These components, represented in Figure 4.2, are associated with different aspects of the cardiac cycle atrial activity, excitation of the ventricles, and repolarization of the ventricles, respectively. 

Figure 1 Electrical gradients in the myocardium can be detected on the body surface ECG. (A) An illustrative example of a single cardiac cycle detected as spatial and temporal electrical gradients on the ECG. The P wave is generated by the spread of excitation through the atria. The QRS complex represents ventricular activation and is followed by the T wave reflecting ventricular repolarization gradients. (B) Schematic representation of cellular electrical activity underlying the ECG [see text and (1) for details]. Arrows indicate the direction of ion flow during each phase of the action potential.

In the SA node, each normal cardiac impulse is initiated by the spontaneous depolarization of the pacemaker cells (see Chapter 34). When a threshold is reached, an action potential is initiated and conducted through the atrial muscle fibers to the AV node and thence through the Purkinje system to the ventricular muscle. ACh slows the heart rate by decreasing the rate of spontaneous diastolic depolarization (the pacemaker current) and by increasing the repolarizing current at the SA node (a direct effect of fiy subunits of G/G, ) in sum, the membrane potential is more negative and attainment of the threshold potential and the succeeding events in the cardiac cycle are delayed. 

Synchronizing the electric charge with the R wave ensures that the current won t be delivered on the vulnerable T wave and disrupts repolarization. This reduces the risk that the current will strike during the relative refractory period of a cardiac cycle and induce VF. 

Six helpful appendices are included Quick guide to cardiac arrhythmias summarizes the details of 20 arrhythmias Cardiac drug overview covers commonly used cardiac drugs Best monitoring leads shows the most beneficial leads to monitor for the most challenging arrhythmias Depolarization-repolarization cycle explains the five phases of this cardiac cycle Action potential curves reviews the cellular changes that occur during the depolarization-repolarization cycle and Cardiac conduction system reviews how electrical impulses affect heart function. 

Class III agents increase the refractoriness of cardiac tissue, thus preventing an aberrant impulse from propagating. A selective Class III agent has little or no effect on simple PVC s. At the cellular level, the increased refractoriness is manifest by a delay in the repolarization phase (Phase 3) of the cardiac action potential Figure 2.1), thereby increasing action potential duration. During the action potential cycle a complex series of ionic currents. 

Electrical activity in the heart can be picked up by electrodes placed on the skin and recorded as the familiar electrocardiogram (ECG). The ECG is a record of the sum of all action potentials in the heart as it contracts. Action potentials are generated by depolarization followed by repolarization of the cardiac muscle cell membrane. Depolarization is initiated by an influx of sodium ions into the cardiac muscle cells, followed by an influx of calcium ions. Repolarization is brought about by efflux of potassium ions. The phases of a cardiac action potential are shown in Eigure 4.3 where the depolarization is the change in resting membrane potential of cardiac muscle cells from —90 mV to 4-20 mV. This is due to influx of sodium ions followed by influx of calcium ions. Contraction of the myocardium follows depolarization. The refractory period is the time interval when a second contraction cannot occur and repolarization is the recovery of the resting potential due to efflux of potassium ions. After this the cycle repeats itself. 

The localization of adducts to the epicardial border zone suggested the possibility that IsoK/LG adducts contribute to cardiac arrhythmias. Ventricular tachycardia/fibrillation following myocardial infarction is a major cause of sudden cardiac death. Arrhythmias in ischemic myocardium arise from sodium channel blockade. Sodium channels are hypothesized to cycle between three conformational states a deactivated closed state, an activated open state, and an inactivated closed state. Upon depolarization, the deactivated state converts to the activated state and sodium current flows for a brief time before the channel enters the inactive state. The channel only converts from the inactive state to the deactivated state when the membrane repolarizes during the falling phase of the action potential. Changes in the ability to convert from the inactive to the deactivated state are critical to the initiation and perpetuation of arrhythmias. 

Conclusions Some antiepileptic drugs, mainly carbamazepine, in particular circumstances, can affect the cardiac repolarization cycle and predispose to SUDEP, but data are still elusive. The susceptibility factors that are most consistently associated with SUDEP include poor seizure control, antiepileptic drug poly therapy, and a long duration of epilepsy [46 ]. In particular, seizure control seems to be of paramount importance in the prevention of SUDEP. In fact, some studies have shown that in a considerable proportion of people with chronic epilepsy, shortly after seizures, some electrocardiographic features occur that may predict an increase in the risk of cardiac mortality or sudden cardiac death [47 ]. Hence, antiepileptic drugs as a class may have a protective effect against SUDEP, since they prevent seizures or reduce their number. 

However, one cannot exclude the possibility that in some patients with epilepsy with a genetic predisposition to cardiac dysrhythmias, the effects of seizures (mainly tonic-clonic seizures) on the repolarization cycle of the heart, and the concomitant effects of some antiepileptic drugs, might cause life-threatening dysrhythmias and possibly SUDEP. 

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