Repolarization

Because both spins are in the transverse plane and transition energy levels are matched, energy can be transferred from the protons to the nuclei. In this manner the rate of repolarization is controlled by rather than by Because the protons can interchange energy by spin-diffusion only a single-proton exists and its value is usually on the order of 1 s. As a result the preparation delay can be reduced from 10 s to about 5 s increasing the number of transients, which can be acquired by two or more orders of magnitude. 

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... 

Glass lA Antiarrhythmic Agents. Class lA antiarrhythmic agents decrease automaticity, ie, depress pacemaker rates, especially ectopic foci rates produce moderate depression of phase 0 depolarization and thus slow conduction in atria, A-V node, His-Purkinje system, and ventricles prolong repolarization, ie, lengthen action potential duration increase refractoriness and depress excitabiHty. These electrophysiological effects are manifested in the ECG by increases in the PR, QRS, and QT intervals. 

Glass IB Antiarrhythmic Agents. Class IB antiarrhythmic agents produce less inhibition of the inward sodium current than Class lA agents. In normal myocardial tissue, phase 0 may be unaffected or minimally depressed. However, in ischemic or infarcted tissue, phase 0 is depressed. Myocardial tissue exposed to Class IB agents exhibits decreased automaticity, shortened action potential duration, ie, shortened repolarization, and shortened refractory period. Excitability of the myocardium is not affected and conduction velocity is increased or not modified. The refractory period is shortened less than its action potential duration, thus the ratio of refractory period to action potential duration is increased by these agents. The net effect is increased refractoriness. The PR and QT intervals of the ECG are shortened and the QRS interval is unchanged (1,2). 

Glass IG Antiarrhythmic Agents. Class IC antiarrhythmic agents have marked local anesthetic effects. They slow the rapid inward sodium current producing marked phase 0 depression and slow conduction. Action potential duration of ventricular muscle is increased, ie, prolonged repolarization, but decreased in the His-Purkinie system by these agents. The effects on the ECG are increased PR interval, marked prolongation of the... 

Fleca.inide, Elecainide acetate, a fluorobenzamide, is a derivative of procainamide, and has been reported to be efficacious in suppressing both supraventricular and ventricular arrhythmias (26—29). The dmg is generally reserved for patients with serious and life-threatening ventricular arrhythmias. Elecainide depresses phase 0 depolarization of the action potential, slows conduction throughout the heart, and significantly prolongs repolarization (30). The latter effect indicates flecainide may possess some Class III antiarrhythmic-type properties (31). 

The variation in the repolarization character causes systematic changes in the properties of the materials. Particularly, the transition from onedimensional structure compounds to three-dimensional structure compounds is accompanied by a decrease in the spontaneous polarization value and in the compound s Curie temperature, and a change in the character of the compound s chemical bonds [390]. 

Antiarrhythmic drugs are substances that affect cardiac ionic channels or receptors, thereby altering the cardiac action potential or its generation or propagation. This results in changes of the spread of activation or the pattern of repolarization. Thereby, these drugs suppress cardiac arrhythmia. 

III Block of repolarizing potassium channels, prolongation of action potential Amiodarone, Dronedarone, Sotalol, Dofetilide, Ibutilide... 

A cell generates late afterdepolarizations (typically induced by catecholamines or digitalis) following a complete repolarization that may elicit an action potential. 

A cell may produce early afterdepolarizations that are depolarization during incomplete repolarization. This is possible if the action potential is considerably prolonged. This is the typical mechanism for elicitation of Torsade de Pointes arrhythmia, a typical complication of class III antiarrhythmics and many other drugs. 

Furthermore, under certain conditions (e.g. local unidirectional block) it is possible that the activation wavefront is delayed and encounters areas already repolarized. This may result in a circulating wave-front (= reentrant circuit reentrant arrhythmia), from which centrifugal activation waves originate and elicit life-threatening ventricular fibrillation. 

Cardiac IKi is the major K+ current responsible for stabilizing the resting membranepotential and shaping the late phase of repolarization of the action potential in cardiac myocytes. The name should not be confused with that of an Intermediate conductance calcium-activated K+ channel, which sometimes is also called IK1. 

Inward Rectifier Potassium Channels or Kir Channels are a class of potassium channels generated by tetra-meiic arrangement of one-pore/two-transmembrane helix (1P/2TM) protein subunits, often associated with additional beta-subunits. Kir channels modulate cell excitability, being involved in repolarization of action potentials (see Fig. 1), setting the resting potential (see Fig. 1) of the cell, and contributing to potassium homeostasis. 

Inward Rectifier K+ Channels. Figure 1 The role of inward rectifier (Kir) channels in cardiac action potentials. Depolarization is generated and maintained by Na and Ca currents (/Na, /Ca). Voltage-gated K currents (Kv) and Kir channels contribute to repolarization and maintenance of a negative resting potential. 

K Channels belong to a class of membrane proteins that form highly K-selective pores in membranes. All known K Channels are composed of several (usually four) pore forming alpha subunits and auxiliary beta subunits. K Channels play an essential role in cellular excitability, being involved in repolarization of Action Potentials and setting the cell resting potential as well as contributing to potassium homeostasis. 

Kvl.5 In human atria, the Kvl.5 presents the ultrarapid delayed rectifier that contributes to the repolarization in the early phase of cardiac action potential. Selective blockers of Kvl.5 channels could be potentially beneficial in the treatment of atrial fibrillation because blocking Kvl. 5 could delay repolarization and prolong refractoriness selectively in cardiac myocytes. Examples for Kvl.5 blockers include AVE0118, S9947, and analogs of diphenyl phosphine oxide (DPO). 

Reentrant arrhythmia occurs when due to inhomogeneous repolarization or unidirectional block, heart tissue which is no longer refractory is close beside tissue which is still activated. This may result in a circuit propagation of activation serving as a reverberator. 

Repolarization is a return of membrane potential to its resting value. It refers mostly to repolarization of an action potential, although a more general meaning of returning a membrane potential back to a more negative value after (forced) depolarization is also common. 

In cerebellar Purkinje cells, a TTX-sensitive inward current is elicited, when the membrane was partially repolarized after strong depolarization. This resurgent current contributes to high-frequency repetitive firing of Purkinje neurons. The resurgent current results from open channel block by the cytoplasmic tail of the (34 subunit. The med Nav 1.6 mutant mice show defective synaptic transmission in the neuromuscular junction and degeneration of cerebellar Purkinje cells. 

In the Long QT Syndrome (LQTS), the repolarization phase of the cardiac muscle is delayed, rendering the heart vulnerable to an arrhythmia known as torsade de pointes. LQTS is associated with five genes encoding ion channels. LQTS type 3 (LQT3) results from mutations of Nav1.5, which cause persistent sodium cunent. In contrast, sodium channel mutations associated with Biugada syndrome reduce the expression level of cardiac sodium channels. 

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